首页 > 最新文献

Open Biology最新文献

英文 中文
Human growth factor-mediated signalling through lipid rafts regulates stem cell proliferation, development and survival of Schistosoma mansoni. 人类生长因子通过脂质筏介导的信号调节曼氏血吸虫干细胞的增殖、发育和存活。
IF 5.8 3区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 Epub Date: 2024-01-10 DOI: 10.1098/rsob.230262
Shradha Maharjan, Ruth S Kirk, Scott P Lawton, Anthony J Walker

Although the mechanisms by which schistosomes grow and develop in humans are poorly defined, their unique outer tegument layer, which interfaces with host blood, is considered vital to homeostasis of the parasite. Here, we investigated the importance of tegument lipid rafts to the biology of Schistosoma mansoni in the context of host-parasite interactions. We demonstrate the temporal clustering of lipid rafts in response to human epidermal growth factor (EGF) during early somule development, concomitant with the localization of anteriorly orientated EGF receptors (EGFRs) and insulin receptors, mapped using fluorescent EGF/insulin ligand. Methyl-β-cyclodextrin (MβCD)-mediated depletion of cholesterol from lipid rafts abrogated the EGFR/IR binding at the parasite surface and led to modulation of protein kinase C, extracellular signal-regulated kinase, p38 mitogen-activated protein kinase and Akt signalling pathways within the parasite. Furthermore, MβCD-mediated lipid raft disruption, and blockade of EGFRs using canertinib, profoundly reduced somule motility and survival, and attenuated stem cell proliferation and somule growth and development particularly to the fast-growing liver stage. These findings provide a novel paradigm for schistosome development and vitality in the host, driven through host-parasite interactions at the tegument, that might be exploitable for developing innovative therapeutic approaches to combat human schistosomiasis.

尽管血吸虫在人体内生长发育的机制尚不十分明确,但其独特的外被膜层与宿主的血液相接,被认为对寄生虫的平衡至关重要。在这里,我们研究了在宿主与寄生虫相互作用的背景下,外膜脂筏对曼氏血吸虫生物学的重要性。我们利用荧光 EGF/胰岛素配体绘制了胰岛素受体(EGFR)和胰岛素受体的定位图。甲基-β-环糊精(MβCD)介导的脂质筏胆固醇耗竭削弱了寄生虫表面的表皮生长因子受体/胰岛素受体结合,并导致寄生虫体内蛋白激酶C、细胞外信号调节激酶、p38丝裂原活化蛋白激酶和Akt信号通路的调节。此外,MβCD介导的脂质筏破坏和使用卡奈替尼阻断表皮生长因子受体可显著降低体细胞的运动性和存活率,并抑制干细胞增殖和体细胞的生长发育,尤其是在快速生长的肝脏阶段。这些发现为血吸虫在宿主体内的发育和活力提供了一种新的范式,这种范式是通过宿主与寄生虫在表皮的相互作用驱动的,可用于开发防治人类血吸虫病的创新治疗方法。
{"title":"Human growth factor-mediated signalling through lipid rafts regulates stem cell proliferation, development and survival of <i>Schistosoma mansoni</i>.","authors":"Shradha Maharjan, Ruth S Kirk, Scott P Lawton, Anthony J Walker","doi":"10.1098/rsob.230262","DOIUrl":"10.1098/rsob.230262","url":null,"abstract":"<p><p>Although the mechanisms by which schistosomes grow and develop in humans are poorly defined, their unique outer tegument layer, which interfaces with host blood, is considered vital to homeostasis of the parasite. Here, we investigated the importance of tegument lipid rafts to the biology of <i>Schistosoma mansoni</i> in the context of host-parasite interactions. We demonstrate the temporal clustering of lipid rafts in response to human epidermal growth factor (EGF) during early somule development, concomitant with the localization of anteriorly orientated EGF receptors (EGFRs) and insulin receptors, mapped using fluorescent EGF/insulin ligand. Methyl-<i>β</i>-cyclodextrin (M<i>β</i>CD)-mediated depletion of cholesterol from lipid rafts abrogated the EGFR/IR binding at the parasite surface and led to modulation of protein kinase C, extracellular signal-regulated kinase, p38 mitogen-activated protein kinase and Akt signalling pathways within the parasite. Furthermore, M<i>β</i>CD-mediated lipid raft disruption, and blockade of EGFRs using canertinib, profoundly reduced somule motility and survival, and attenuated stem cell proliferation and somule growth and development particularly to the fast-growing liver stage. These findings provide a novel paradigm for schistosome development and vitality in the host, driven through host-parasite interactions at the tegument, that might be exploitable for developing innovative therapeutic approaches to combat human schistosomiasis.</p>","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10776228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A critical threshold of MCM10 is required to maintain genome stability during differentiation of induced pluripotent stem cells into natural killer cells. 在诱导多能干细胞分化为自然杀伤细胞的过程中,需要一个临界阈值的 MCM10 来维持基因组的稳定性。
IF 4.5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 Epub Date: 2024-01-24 DOI: 10.1098/rsob.230407
Megan M Schmit, Ryan M Baxley, Liangjun Wang, Peter Hinderlie, Marissa Kaufman, Emily Simon, Anjali Raju, Jeffrey S Miller, Anja-Katrin Bielinsky

Natural killer (NK) cell deficiency (NKD) is a rare disease in which NK cell function is reduced, leaving affected individuals susceptible to repeated viral infections and cancer. Recently, a patient with NKD was identified carrying compound heterozygous variants of MCM10 (minichromosome maintenance protein 10), an essential gene required for DNA replication, that caused a significant decrease in the amount of functional MCM10. NKD in this patient presented as loss of functionally mature late-stage NK cells. To understand how MCM10 deficiency affects NK cell development, we generated MCM10 heterozygous (MCM10+/-) induced pluripotent stem cell (iPSC) lines. Analyses of these cell lines demonstrated that MCM10 was haploinsufficient, similar to results in other human cell lines. Reduced levels of MCM10 in mutant iPSCs was associated with impaired clonogenic survival and increased genomic instability, including micronuclei formation and telomere erosion. The severity of these phenotypes correlated with the extent of MCM10 depletion. Significantly, MCM10+/- iPSCs displayed defects in NK cell differentiation, exhibiting reduced yields of hematopoietic stem cells (HSCs). Although MCM10+/- HSCs were able to give rise to lymphoid progenitors, these did not generate mature NK cells. The lack of mature NK cells coincided with telomere erosion, suggesting that NKD caused by these MCM10 variants arose from the accumulation of genomic instability including degradation of chromosome ends.

自然杀伤(NK)细胞缺乏症(NKD)是一种罕见的疾病,NK 细胞功能降低,使患者容易反复感染病毒和患癌症。最近,发现一名 NKD 患者携带 DNA 复制所需的重要基因 MCM10(迷你染色体维护蛋白 10)的复合杂合变体,导致功能性 MCM10 的数量显著减少。该患者的 NKD 表现为功能成熟的晚期 NK 细胞丧失。为了了解 MCM10 缺乏如何影响 NK 细胞的发育,我们生成了 MCM10 杂合子(MCM10+/-)诱导多能干细胞(iPSC)系。对这些细胞系的分析表明,MCM10 是单倍体,这与其他人类细胞系的结果相似。突变型 iPSC 中 MCM10 水平的降低与克隆生成存活率受损和基因组不稳定性增加(包括微核形成和端粒侵蚀)有关。这些表型的严重程度与 MCM10 的消耗程度相关。值得注意的是,MCM10+/- iPSCs 显示出 NK 细胞分化缺陷,造血干细胞(HSCs)产量减少。虽然 MCM10+/- 造血干细胞能产生淋巴祖细胞,但这些祖细胞不能生成成熟的 NK 细胞。成熟 NK 细胞的缺乏与端粒侵蚀同时发生,这表明这些 MCM10 变体导致的 NKD 是由基因组不稳定性(包括染色体末端退化)的积累引起的。
{"title":"A critical threshold of MCM10 is required to maintain genome stability during differentiation of induced pluripotent stem cells into natural killer cells.","authors":"Megan M Schmit, Ryan M Baxley, Liangjun Wang, Peter Hinderlie, Marissa Kaufman, Emily Simon, Anjali Raju, Jeffrey S Miller, Anja-Katrin Bielinsky","doi":"10.1098/rsob.230407","DOIUrl":"10.1098/rsob.230407","url":null,"abstract":"<p><p>Natural killer (NK) cell deficiency (NKD) is a rare disease in which NK cell function is reduced, leaving affected individuals susceptible to repeated viral infections and cancer. Recently, a patient with NKD was identified carrying compound heterozygous variants of <i>MCM10</i> (<i>minichromosome maintenance protein 10</i>), an essential gene required for DNA replication, that caused a significant decrease in the amount of functional MCM10. NKD in this patient presented as loss of functionally mature late-stage NK cells. To understand how MCM10 deficiency affects NK cell development, we generated <i>MCM10</i> heterozygous (<i>MCM10<sup>+/-</sup></i>) induced pluripotent stem cell (iPSC) lines. Analyses of these cell lines demonstrated that <i>MCM10</i> was haploinsufficient, similar to results in other human cell lines. Reduced levels of MCM10 in mutant iPSCs was associated with impaired clonogenic survival and increased genomic instability, including micronuclei formation and telomere erosion. The severity of these phenotypes correlated with the extent of MCM10 depletion. Significantly, <i>MCM10<sup>+/-</sup></i> iPSCs displayed defects in NK cell differentiation, exhibiting reduced yields of hematopoietic stem cells (HSCs). Although <i>MCM10<sup>+/-</sup></i> HSCs were able to give rise to lymphoid progenitors, these did not generate mature NK cells. The lack of mature NK cells coincided with telomere erosion, suggesting that NKD caused by these <i>MCM10</i> variants arose from the accumulation of genomic instability including degradation of chromosome ends.</p>","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10805602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139542632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deficiency of the ribosomal protein uS10 (RPS20) reorganizes human cells translatome according to the abundance, CDS length and GC content of mRNAs. 核糖体蛋白uS10(RPS20)的缺乏会根据mRNA的丰度、CDS长度和GC含量重组人体细胞的翻译组。
IF 4.5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 Epub Date: 2024-01-31 DOI: 10.1098/rsob.230366
Yueming Tian, Elena S Babaylova, Alexander V Gopanenko, Alexey E Tupikin, Marsel R Kabilov, Alexey A Malygin

Ribosomal protein uS10, a product of the RPS20 gene, is an essential constituent of the small (40S) subunit of the human ribosome. Disruptive mutations in its gene are associated with a predisposition to hereditary colorectal carcinoma. Here, using HEK293T cells, we show that a deficiency of this protein leads to a decrease in the level of ribosomes (ribosomal shortage). RNA sequencing of the total and polysome-associated mRNA samples reveals hundreds of genes differentially expressed in the transcriptome (t)DEGs and translatome (p)DEGs under conditions of uS10 deficiency. We demonstrate that the (t)DEG and (p)DEG sets partially overlap, determine genes with altered translational efficiency (TE) and identify cellular processes affected by uS10 deficiency-induced ribosomal shortage. We reveal that translated mRNAs of upregulated (p)DEGs and genes with altered TE in uS10-deficient cells are generally more abundant and that their GC contents are significantly lower than those of the respective downregulated sets. We also observed that upregulated (p)DEGs have longer coding sequences. Based on our findings, we propose a combinatorial model describing the process of reorganization of mRNA translation under conditions of ribosomal shortage. Our results reveal rules according to which ribosomal shortage reorganizes the transcriptome and translatome repertoires of actively proliferating cells.

核糖体蛋白 uS10 是 RPS20 基因的产物,是人类核糖体小亚基(40S)的重要组成部分。其基因的破坏性突变与遗传性结直肠癌的易感性有关。在这里,我们利用 HEK293T 细胞证明,缺乏这种蛋白质会导致核糖体水平下降(核糖体缺乏)。总mRNA和多聚体相关mRNA样本的RNA测序显示,在uS10缺乏的条件下,数百个基因在转录组(t)DEG和转译组(p)DEG中差异表达。我们证明(t)DEG和(p)DEG集部分重叠,确定了翻译效率(TE)改变的基因,并确定了受uS10缺乏引起的核糖体短缺影响的细胞过程。我们发现,在uS10缺乏的细胞中,上调(p)DEG和TE改变的基因的翻译mRNA通常更丰富,其GC含量明显低于相应的下调集。我们还观察到,上调(p)DEGs 的编码序列较长。根据我们的研究结果,我们提出了一个组合模型,描述了核糖体短缺条件下 mRNA 翻译的重组过程。我们的研究结果揭示了核糖体短缺重组活跃增殖细胞转录组和翻译组的规则。
{"title":"Deficiency of the ribosomal protein uS10 (RPS20) reorganizes human cells translatome according to the abundance, CDS length and GC content of mRNAs.","authors":"Yueming Tian, Elena S Babaylova, Alexander V Gopanenko, Alexey E Tupikin, Marsel R Kabilov, Alexey A Malygin","doi":"10.1098/rsob.230366","DOIUrl":"10.1098/rsob.230366","url":null,"abstract":"<p><p>Ribosomal protein uS10, a product of the <i>RPS20</i> gene, is an essential constituent of the small (40S) subunit of the human ribosome. Disruptive mutations in its gene are associated with a predisposition to hereditary colorectal carcinoma. Here, using HEK293T cells, we show that a deficiency of this protein leads to a decrease in the level of ribosomes (ribosomal shortage). RNA sequencing of the total and polysome-associated mRNA samples reveals hundreds of genes differentially expressed in the transcriptome (t)DEGs and translatome (p)DEGs under conditions of uS10 deficiency. We demonstrate that the (t)DEG and (p)DEG sets partially overlap, determine genes with altered translational efficiency (TE) and identify cellular processes affected by uS10 deficiency-induced ribosomal shortage. We reveal that translated mRNAs of upregulated (p)DEGs and genes with altered TE in uS10-deficient cells are generally more abundant and that their GC contents are significantly lower than those of the respective downregulated sets. We also observed that upregulated (p)DEGs have longer coding sequences. Based on our findings, we propose a combinatorial model describing the process of reorganization of mRNA translation under conditions of ribosomal shortage. Our results reveal rules according to which ribosomal shortage reorganizes the transcriptome and translatome repertoires of actively proliferating cells.</p>","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10827436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Serum amyloid P component accumulates and persists in neurones following traumatic brain injury. 脑外伤后,血清中的淀粉样蛋白 P 成分会在神经元中累积并持续存在。
IF 5.8 3区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-01 Epub Date: 2023-12-06 DOI: 10.1098/rsob.230253
Ping K Yip, Zhou-Hao Liu, Shumaila Hasan, Mark B Pepys, Christopher E G Uff

The mechanisms underlying neurodegenerative sequelae of traumatic brain injury (TBI) are poorly understood. The normal plasma protein, serum amyloid P component (SAP), which is normally rigorously excluded from the brain, is directly neurocytotoxic for cerebral neurones and also binds to Aβ amyloid fibrils and neurofibrillary tangles, promoting formation and persistence of Aβ fibrils. Increased brain exposure to SAP is common to many risk factors for dementia, including TBI, and dementia at death in the elderly is significantly associated with neocortical SAP content. Here, in 18 of 30 severe TBI cases, we report immunohistochemical staining for SAP in contused brain tissue with blood-brain barrier disruption. The SAP was localized to neurofilaments in a subset of neurones and their processes, particularly damaged axons and cell bodies, and was present regardless of the time after injury. No SAP was detected on astrocytes, microglia, cerebral capillaries or serotoninergic neurones and was absent from undamaged brain. C-reactive protein, the control plasma protein most closely similar to SAP, was only detected within capillary lumina. The appearance of neurocytotoxic SAP in the brain after TBI, and its persistent, selective deposition in cerebral neurones, are consistent with a potential contribution to subsequent neurodegeneration.

人们对创伤性脑损伤(TBI)导致神经退行性后遗症的机制知之甚少。正常血浆蛋白--血清淀粉样蛋白 P 成分(SAP)通常被严格排除在大脑之外,但它对大脑神经元具有直接的神经细胞毒性,还能与 Aβ 淀粉样纤维和神经纤维缠结结合,促进 Aβ 纤维的形成和持续存在。包括创伤性脑损伤在内的许多痴呆症风险因素都会增加大脑对SAP的暴露,而老年人死亡时的痴呆症与新皮质中SAP的含量显著相关。在此,我们对 30 例严重创伤性脑损伤病例中的 18 例进行了 SAP 免疫组织化学染色。SAP 定位于一部分神经元及其过程的神经丝,尤其是受损的轴突和细胞体,并且与损伤后的时间无关。在星形胶质细胞、小胶质细胞、脑毛细血管或5-羟色胺能神经元中均未检测到SAP,未受损的大脑中也不存在SAP。与 SAP 最为相似的对照血浆蛋白 C 反应蛋白仅在毛细血管管腔内被检测到。创伤性脑损伤后大脑中出现的神经细胞毒性 SAP 及其在大脑神经元中的持续、选择性沉积与随后的神经变性的潜在作用是一致的。
{"title":"Serum amyloid P component accumulates and persists in neurones following traumatic brain injury.","authors":"Ping K Yip, Zhou-Hao Liu, Shumaila Hasan, Mark B Pepys, Christopher E G Uff","doi":"10.1098/rsob.230253","DOIUrl":"10.1098/rsob.230253","url":null,"abstract":"<p><p>The mechanisms underlying neurodegenerative sequelae of traumatic brain injury (TBI) are poorly understood. The normal plasma protein, serum amyloid P component (SAP), which is normally rigorously excluded from the brain, is directly neurocytotoxic for cerebral neurones and also binds to A<i>β</i> amyloid fibrils and neurofibrillary tangles, promoting formation and persistence of A<i>β</i> fibrils. Increased brain exposure to SAP is common to many risk factors for dementia, including TBI, and dementia at death in the elderly is significantly associated with neocortical SAP content. Here, in 18 of 30 severe TBI cases, we report immunohistochemical staining for SAP in contused brain tissue with blood-brain barrier disruption. The SAP was localized to neurofilaments in a subset of neurones and their processes, particularly damaged axons and cell bodies, and was present regardless of the time after injury. No SAP was detected on astrocytes, microglia, cerebral capillaries or serotoninergic neurones and was absent from undamaged brain. C-reactive protein, the control plasma protein most closely similar to SAP, was only detected within capillary lumina. The appearance of neurocytotoxic SAP in the brain after TBI, and its persistent, selective deposition in cerebral neurones, are consistent with a potential contribution to subsequent neurodegeneration.</p>","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10697800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138488215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
LIM-HD transcription factors control axial patterning and specify distinct neuronal and intestinal cell identities in planarians LIM-HD转录因子控制轴向模式化,并指定扁形动物中不同的神经细胞和肠细胞特性
IF 5.8 3区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-01 DOI: 10.1098/rsob.230327
M. D. Molina, Dema Abduljabbar, Anna Guixeras, S. Fraguas, F. Cebrià
Adult planarians can regenerate the gut, eyes and even a functional brain. Proper identity and patterning of the newly formed structures require signals that guide and commit their adult stem cells. During embryogenesis, LIM-homeodomain (LIM-HD) transcription factors act in a combinatorial ‘LIM code’ to control cell fate determination and differentiation. However, our understanding about the role these genes play during regeneration and homeostasis is limited. Here, we report the full repertoire of LIM-HD genes in Schmidtea mediterranea. We found that lim homeobox (lhx) genes appear expressed in complementary patterns along the cephalic ganglia and digestive system of the planarian, with some of them being co-expressed in the same cell types. We have identified that Smed-islet1, -lhx1/5-1, -lhx2/9-3, -lhx6/8, -lmx1a/b-2 and -lmx1a/b-3 are essential to pattern and size the planarian brain as well as for correct regeneration of specific subpopulations of dopaminergic, serotonergic, GABAergic and cholinergic neurons, while Smed-lhx1/5.2 and -lhx2/9.2 are required for the proper expression of intestinal cell type markers, specifically the goblet subtype. LIM-HD are also involved in controlling axonal pathfinding (lhx6/8), axial patterning (islet1, lhx1/5-1, lmx1a/b-3), head/body proportions (islet2) and stem cell proliferation (lhx3/4, lhx2/9-3, lmx1a/b-2, lmx1a/b-3). Altogether, our results suggest that planarians might present a combinatorial LIM code that controls axial patterning and axonal growing and specifies distinct neuronal and intestinal cell identities.
成年涡虫可以再生肠道、眼睛,甚至有功能的大脑。新形成的结构的正确识别和模式需要引导和投入成体干细胞的信号。在胚胎发生过程中,LIM同源结构域(LIM- hd)转录因子在一个组合的“LIM代码”中起作用,控制细胞命运的决定和分化。然而,我们对这些基因在再生和体内平衡过程中所起的作用的了解是有限的。在这里,我们报道了地中海施米德亚(Schmidtea mediterranea)中LIM-HD基因的全部曲目。我们发现,在涡虫的头神经节和消化系统中,许多同源盒(lhx)基因以互补的模式表达,其中一些基因在相同的细胞类型中共表达。我们已经发现,smmed -islet1、-lhx1/5-1、-lhx2/9-3、-lhx2/ 6/8、-lmx1a/b-2和-lmx1a/b-3对于规划和大小以及多巴胺能、血清素能、gaba能和胆碱能神经元特定亚群的正确再生是必不可少的,而smmed -lhx1/5.2和-lhx2/9.2对于肠道细胞类型标记物的正确表达是必需的,特别是杯状亚型。LIM-HD还参与控制轴突寻路(lhx6/8),轴向模式(islet1, lhx1/5-1, lmx1a/b-3),头/体比例(islet2)和干细胞增殖(lhx3/4, lhx2/9-3, lmx1a/b-2, lmx1a/b-3)。总之,我们的研究结果表明,涡虫可能存在一个组合的LIM代码,控制轴向模式和轴突生长,并指定不同的神经元和肠细胞身份。
{"title":"LIM-HD transcription factors control axial patterning and specify distinct neuronal and intestinal cell identities in planarians","authors":"M. D. Molina, Dema Abduljabbar, Anna Guixeras, S. Fraguas, F. Cebrià","doi":"10.1098/rsob.230327","DOIUrl":"https://doi.org/10.1098/rsob.230327","url":null,"abstract":"Adult planarians can regenerate the gut, eyes and even a functional brain. Proper identity and patterning of the newly formed structures require signals that guide and commit their adult stem cells. During embryogenesis, LIM-homeodomain (LIM-HD) transcription factors act in a combinatorial ‘LIM code’ to control cell fate determination and differentiation. However, our understanding about the role these genes play during regeneration and homeostasis is limited. Here, we report the full repertoire of LIM-HD genes in Schmidtea mediterranea. We found that lim homeobox (lhx) genes appear expressed in complementary patterns along the cephalic ganglia and digestive system of the planarian, with some of them being co-expressed in the same cell types. We have identified that Smed-islet1, -lhx1/5-1, -lhx2/9-3, -lhx6/8, -lmx1a/b-2 and -lmx1a/b-3 are essential to pattern and size the planarian brain as well as for correct regeneration of specific subpopulations of dopaminergic, serotonergic, GABAergic and cholinergic neurons, while Smed-lhx1/5.2 and -lhx2/9.2 are required for the proper expression of intestinal cell type markers, specifically the goblet subtype. LIM-HD are also involved in controlling axonal pathfinding (lhx6/8), axial patterning (islet1, lhx1/5-1, lmx1a/b-3), head/body proportions (islet2) and stem cell proliferation (lhx3/4, lhx2/9-3, lmx1a/b-2, lmx1a/b-3). Altogether, our results suggest that planarians might present a combinatorial LIM code that controls axial patterning and axonal growing and specifies distinct neuronal and intestinal cell identities.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138610360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The role of cilia during organogenesis in zebrafish. 纤毛在斑马鱼器官形成过程中的作用
IF 5.8 3区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-01 Epub Date: 2023-12-13 DOI: 10.1098/rsob.230228
Junjun Liu, Haibo Xie, Mengfan Wu, Yidan Hu, Yunsi Kang

Cilia are hair-like organelles that protrude from the surface of eukaryotic cells and are present on the surface of nearly all human cells. Cilia play a crucial role in signal transduction, organ development and tissue homeostasis. Abnormalities in the structure and function of cilia can lead to a group of human diseases known as ciliopathies. Currently, zebrafish serves as an ideal model for studying ciliary function and ciliopathies due to its relatively conserved structure and function of cilia compared to humans. In this review, we will summarize the different types of cilia that present in embryonic and adult zebrafish, and provide an overview of the advantages of using zebrafish as a vertebrate model for cilia research. We will specifically focus on the roles of cilia during zebrafish organogenesis based on recent studies. Additionally, we will highlight future prospects for ciliary research in zebrafish.

纤毛是从真核细胞表面伸出的毛发状细胞器,几乎存在于所有人类细胞的表面。纤毛在信号转导、器官发育和组织稳态中起着至关重要的作用。纤毛结构和功能异常可导致一组人类疾病,即纤毛疾病。目前,斑马鱼是研究纤毛功能和纤毛疾病的理想模型,因为与人类相比,斑马鱼的纤毛结构和功能相对保守。在这篇综述中,我们将总结存在于斑马鱼胚胎和成体中的不同类型的纤毛,并概述使用斑马鱼作为脊椎动物模型进行纤毛研究的优势。我们将根据最近的研究,特别关注纤毛在斑马鱼器官形成过程中的作用。此外,我们还将强调斑马鱼纤毛研究的未来前景。
{"title":"The role of cilia during organogenesis in zebrafish.","authors":"Junjun Liu, Haibo Xie, Mengfan Wu, Yidan Hu, Yunsi Kang","doi":"10.1098/rsob.230228","DOIUrl":"https://doi.org/10.1098/rsob.230228","url":null,"abstract":"<p><p>Cilia are hair-like organelles that protrude from the surface of eukaryotic cells and are present on the surface of nearly all human cells. Cilia play a crucial role in signal transduction, organ development and tissue homeostasis. Abnormalities in the structure and function of cilia can lead to a group of human diseases known as ciliopathies. Currently, zebrafish serves as an ideal model for studying ciliary function and ciliopathies due to its relatively conserved structure and function of cilia compared to humans. In this review, we will summarize the different types of cilia that present in embryonic and adult zebrafish, and provide an overview of the advantages of using zebrafish as a vertebrate model for cilia research. We will specifically focus on the roles of cilia during zebrafish organogenesis based on recent studies. Additionally, we will highlight future prospects for ciliary research in zebrafish.</p>","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10715920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138807556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mitochondrial replication's role in vertebrate mtDNA strand asymmetry. 线粒体复制在脊椎动物 mtDNA 链不对称中的作用。
IF 5.8 3区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-01 Epub Date: 2023-12-20 DOI: 10.1098/rsob.230181
André Gomes-Dos-Santos, Nair Vilas-Arrondo, André M Machado, Esther Román-Marcote, Jose Luís Del Río Iglesias, Francisco Baldó, Montse Pérez, Miguel M Fonseca, L Filipe C Castro, Elsa Froufe

Mitogenomes are defined as compact and structurally stable over aeons. This perception results from a vertebrate-centric vision, where few types of mtDNA rearrangements are described. Here, we bring a new light to the involvement of mitochondrial replication in the strand asymmetry of the vertebrate mtDNA. Using several species of deep-sea hatchetfish (Sternoptychidae) displaying distinct mtDNA structural arrangements, we unravel the inversion of the coding direction of protein-coding genes (PCGs). This unexpected change is coupled with a strand asymmetry nucleotide composition reversal and is shown to be directly related to the strand location of the Control Region (CR). An analysis of the fourfold redundant sites of the PCGs (greater than 6000 vertebrates), revealed the rarity of this phenomenon, found in nine fish species (five deep-sea hatchetfish). Curiously, in Antarctic notothenioid fishes (Trematominae), where a single PCG inversion (the only other record in fish) is coupled with the inversion of the CR, the standard asymmetry is disrupted for the remaining PCGs but not yet reversed, suggesting a transitory state. Our results hint that a relaxation of the classic vertebrate mitochondrial structural stasis promotes disruption of the natural balance of asymmetry of the mtDNA. These findings support the long-lasting hypothesis that replication is the main molecular mechanism promoting the strand-specific compositional bias of this unique and indispensable molecule.

有丝分裂基因组被定义为结构紧凑、结构稳定、历经漫长岁月的基因组。这种看法源于以脊椎动物为中心的视角,其中描述的 mtDNA 重排类型很少。在这里,我们为线粒体复制参与脊椎动物 mtDNA 链不对称带来了新的启示。我们利用几种表现出不同 mtDNA 结构排列的深海箭鱼(Sternoptychidae),揭示了蛋白质编码基因(PCGs)编码方向的反转。这一意想不到的变化与链不对称核苷酸组成反转有关,并被证明与控制区(CR)的链位置直接相关。对 PCGs 的四倍冗余位点(超过 6000 种脊椎动物)的分析表明,这种现象在九种鱼类(五种深海棘鱼)中非常罕见。奇怪的是,在南极蝾螈科鱼类(Trematominae)中,单个 PCG 反转(鱼类中唯一的其他记录)与 CR 反转同时发生,标准不对称在剩余 PCG 中被破坏,但尚未逆转,这表明这是一种过渡状态。我们的研究结果表明,脊椎动物线粒体经典结构停滞的松弛会破坏 mtDNA 不对称的自然平衡。这些发现支持了一个由来已久的假设,即复制是促进这一独特且不可或缺的分子链特异性组成偏向的主要分子机制。
{"title":"Mitochondrial replication's role in vertebrate mtDNA strand asymmetry.","authors":"André Gomes-Dos-Santos, Nair Vilas-Arrondo, André M Machado, Esther Román-Marcote, Jose Luís Del Río Iglesias, Francisco Baldó, Montse Pérez, Miguel M Fonseca, L Filipe C Castro, Elsa Froufe","doi":"10.1098/rsob.230181","DOIUrl":"10.1098/rsob.230181","url":null,"abstract":"<p><p>Mitogenomes are defined as compact and structurally stable over aeons. This perception results from a vertebrate-centric vision, where few types of mtDNA rearrangements are described. Here, we bring a new light to the involvement of mitochondrial replication in the strand asymmetry of the vertebrate mtDNA. Using several species of deep-sea hatchetfish (Sternoptychidae) displaying distinct mtDNA structural arrangements, we unravel the inversion of the coding direction of protein-coding genes (PCGs). This unexpected change is coupled with a strand asymmetry nucleotide composition reversal and is shown to be directly related to the strand location of the Control Region (CR). An analysis of the fourfold redundant sites of the PCGs (greater than 6000 vertebrates), revealed the rarity of this phenomenon, found in nine fish species (five deep-sea hatchetfish). Curiously, in Antarctic notothenioid fishes (Trematominae), where a single PCG inversion (the only other record in fish) is coupled with the inversion of the CR, the standard asymmetry is disrupted for the remaining PCGs but not yet reversed, suggesting a transitory state. Our results hint that a relaxation of the classic vertebrate mitochondrial structural <i>stasis</i> promotes disruption of the natural balance of asymmetry of the mtDNA. These findings support the long-lasting hypothesis that replication is the main molecular mechanism promoting the strand-specific compositional bias of this unique and indispensable molecule.</p>","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10730292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138807554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Retraction: 'Long non-coding RNA LINC00467 regulates hepatocellular carcinoma progression by modulating miR-9-5p/PPARA expression' (2019), by Cai et al. 撤回:“长非编码RNA LINC00467通过调节miR-9-5p/PPARA的表达来调节肝细胞癌的进展”(2019),Cai等人。
IF 5.8 3区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-11-01 Epub Date: 2023-11-03 DOI: 10.1098/rsob.230405
{"title":"Retraction: 'Long non-coding RNA LINC00467 regulates hepatocellular carcinoma progression by modulating miR-9-5p/PPARA expression' (2019), by Cai <i>et al.</i>","authors":"","doi":"10.1098/rsob.230405","DOIUrl":"10.1098/rsob.230405","url":null,"abstract":"","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71434437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Retraction: 'MALAT1 promotes gastric adenocarcinoma through the MALAT1/miR-181a-5p/AKT3 axis' (2019), by Lu et al. 回缩:Lu等人的“MALAT1通过MALAT1/miR-181a-5p/AKT3轴促进胃腺癌”(2019)。
IF 5.8 3区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-11-01 Epub Date: 2023-11-03 DOI: 10.1098/rsob.230404
{"title":"Retraction: 'MALAT1 promotes gastric adenocarcinoma through the MALAT1/miR-181a-5p/AKT3 axis' (2019), by Lu <i>et al.</i>","authors":"","doi":"10.1098/rsob.230404","DOIUrl":"10.1098/rsob.230404","url":null,"abstract":"","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71434438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genome editing in East African cichlids and tilapias: state-of-the-art and future directions. 东非慈鲷和罗非鱼的基因组编辑:最新技术和未来方向。
IF 5.8 3区 生物学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-11-01 Epub Date: 2023-11-29 DOI: 10.1098/rsob.230257
Bethan Clark, Muktai Kuwalekar, Bettina Fischer, Joost Woltering, Jakob Biran, Scott Juntti, Claudius F Kratochwil, M Emília Santos, Miguel Vasconcelos Almeida

African cichlid fishes of the Cichlidae family are a group of teleosts important for aquaculture and research. A thriving research community is particularly interested in the cichlid radiations of the East African Great Lakes. One key goal is to pinpoint genetic variation underlying phenotypic diversification, but the lack of genetic tools has precluded thorough dissection of the genetic basis of relevant traits in cichlids. Genome editing technologies are well established in teleost models like zebrafish and medaka. However, this is not the case for emerging model organisms, such as East African cichlids, where these technologies remain inaccessible to most laboratories, due in part to limited exchange of knowledge and expertise. The Cichlid Science 2022 meeting (Cambridge, UK) hosted for the first time a Genome Editing Workshop, where the community discussed recent advances in genome editing, with an emphasis on CRISPR/Cas9 technologies. Based on the workshop findings and discussions, in this review we define the state-of-the-art of cichlid genome editing, share resources and protocols, and propose new possible avenues to further expand the cichlid genome editing toolkit.

非洲慈鲷科的慈鲷是一类对水产养殖和研究具有重要意义的硬骨鱼。一个蓬勃发展的研究界对东非大湖的慈鲷辐射特别感兴趣。一个关键目标是确定表型多样化的遗传变异,但缺乏遗传工具阻碍了对慈鲷相关性状遗传基础的彻底解剖。基因组编辑技术已经在斑马鱼和medaka等硬骨鱼模型中得到了很好的应用。然而,对于新兴的模式生物,例如东非慈鲷,情况并非如此,在那里,大多数实验室仍然无法获得这些技术,部分原因是知识和专业知识的交流有限。2022年慈鲷科学会议(Cambridge, UK)首次举办了基因组编辑研讨会,会上,科学界讨论了基因组编辑的最新进展,重点是CRISPR/Cas9技术。基于本次研讨会的成果和讨论,本文综述了慈鲷基因组编辑的最新进展,分享了资源和协议,并提出了进一步扩展慈鲷基因组编辑工具包的新途径。
{"title":"Genome editing in East African cichlids and tilapias: state-of-the-art and future directions.","authors":"Bethan Clark, Muktai Kuwalekar, Bettina Fischer, Joost Woltering, Jakob Biran, Scott Juntti, Claudius F Kratochwil, M Emília Santos, Miguel Vasconcelos Almeida","doi":"10.1098/rsob.230257","DOIUrl":"10.1098/rsob.230257","url":null,"abstract":"<p><p>African cichlid fishes of the Cichlidae family are a group of teleosts important for aquaculture and research. A thriving research community is particularly interested in the cichlid radiations of the East African Great Lakes. One key goal is to pinpoint genetic variation underlying phenotypic diversification, but the lack of genetic tools has precluded thorough dissection of the genetic basis of relevant traits in cichlids. Genome editing technologies are well established in teleost models like zebrafish and medaka. However, this is not the case for emerging model organisms, such as East African cichlids, where these technologies remain inaccessible to most laboratories, due in part to limited exchange of knowledge and expertise. The Cichlid Science 2022 meeting (Cambridge, UK) hosted for the first time a Genome Editing Workshop, where the community discussed recent advances in genome editing, with an emphasis on CRISPR/Cas9 technologies. Based on the workshop findings and discussions, in this review we define the state-of-the-art of cichlid genome editing, share resources and protocols, and propose new possible avenues to further expand the cichlid genome editing toolkit.</p>","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10685126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138452009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Open Biology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1