Differentiation最新文献_第3页

Inhibition of Atg13-mediated autophagy enhances the anti-osteoclastogenic effect of sirolimus by counteracting its pro-autophagic activity 抑制atg13介导的自噬可通过抵消西罗莫司的促自噬活性来增强其抗破骨细胞作用

IF 2.6 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2025-08-23 DOI: 10.1016/j.diff.2025.100902

Tingwei Gao , Jiankun Wang , Jiajia Wang , Xi Li , Zhanhao Xiao

Sirolimus can inhibit osteoclastogenesis. But sirolimus-activated autophagy is a favorable factor for osteoclastogenesis. This study aimed to explore the significance of autophagy in sirolimus-regulated osteoclastogenesis. Our results confirmed that sirolimus inhibited osteoclastic differentiation (including the number and size of osteoclasts as well as the expression of osteoclastic genes) and promotes osteoclast precursor (OCP) autophagy (including LC3 conversion and autophagosome/autolysosome formation). As expected, OCP autophagy (including LC3 conversion and LC3-puncta formation) promoted by sirolimus was reversed by autophagy inactivation with 3-MA or Atg13 silencing. Importantly, compared with single intervention of sirolimus, the combination of sirolimus and 3-MA or Atg13 silencing more effectively inhibited osteoclastic differentiation and OCP proliferation. In vivo experiments also demonstrated that the combination of sirolimus and Atg13-silencing adeno-associated viruses (AAVs) was more effective than sirolimus alone in improving decreased bone density and damaged bone microstructure (including Micro-CT imaging results, bone tissue parameters and trabecular area), and attenuating osteoclastic activity (including the abundance of osteoclasts in trabecular bones and the production of osteoclastic markers in serum) in ovariectomized (OVX) mice. In conclusion, repressing Atg13-related autophagy can effectively enhance the function of sirolimus in inhibiting osteoclastogenesis by counteracting its pro-autophagic activity. Therefore, the combination of sirolimus and Atg13-targeting therapy is expected to enhance the efficacy of sirolimus in ameliorating osteoclastic osteoporosis.

西罗莫司能抑制破骨细胞的发生。但西罗莫司激活的自噬是破骨细胞发生的有利因素。本研究旨在探讨自噬在西罗莫司调节的破骨细胞发生中的意义。我们的研究结果证实西罗莫司抑制破骨细胞分化（包括破骨细胞的数量和大小以及破骨基因的表达），促进破骨细胞前体（OCP）自噬（包括LC3转化和自噬体/自噬体的形成）。正如预期的那样，西罗莫司促进的OCP自噬（包括LC3转化和LC3点形成）通过3-MA或Atg13沉默的自噬失活被逆转。重要的是，与西罗莫司单独干预相比，西罗莫司联合3-MA或Atg13沉默更有效地抑制破骨细胞分化和OCP增殖。体内实验还表明，西罗莫司和atg13沉默腺相关病毒（aav）联合使用在改善卵巢切除（OVX）小鼠骨密度下降和受损骨微观结构（包括显微ct成像结果、骨组织参数和小梁面积）以及降低破骨活性（包括小梁骨中破骨细胞的丰度和血清中破骨标志物的产生）方面比西罗莫司单独使用更有效。综上所述，抑制atg13相关自噬可通过抵消西罗莫司的促自噬活性，有效增强西罗莫司抑制破骨细胞生成的功能。因此，西罗莫司联合atg13靶向治疗有望增强西罗莫司改善破骨性骨质疏松症的疗效。

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引用次数: 0

NONO regulates monocyte-macrophage lineage differentiation through a potential PI3K/AKT-dependent mechanism NONO通过潜在的PI3K/ akt依赖机制调节单核-巨噬细胞谱系分化

IF 2.6 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2025-08-20 DOI: 10.1016/j.diff.2025.100901

Xiu-Rong Wei , Dan Hu , Zi-Jiang Yang , Lv-Bin Yan , Guang-Yu Xu , Rui-Gang Zhang , Xiu-Juan Zhang

Non-POU domain containing octamer binding protein (NONO) is a multifunctional nuclear protein which plays important roles in regulating nuclear processes such as transcription and splicing. We aimed to delineate the effects and the underlying mechanisms of NONO on monocyte-macrophage lineage differentiation. By depolying a phorbol 12-myristate 13-acetate (PMA)-induced THP-1 cell differentiation model and a macrophage colony-stimulating factor (M-CSF)-induced mouse bone marrow cell differentiation model, we examined the expression pattern and the effects of NONO during monocyte-macrophage lineage differentiation. The research revealed that the expression of NONO protein progressively decreased during the M-CSF-induced differentiation of mouse bone marrow cells into macrophages and the PMA-induced differentiation of THP-1 human monocytic leukemia cells into macrophages. The monocyte-macrophage lineage differentiation process was enhanced in Nono gene knockout (Nono K.O.) mouse bone marrow cells as well as NONO knockdown (NONO K.D.) THP-1 cells. The study also found that reduced NONO expression enhanced the AKT phosphorylation during macrophage lineage differentiation. At the same time, the PI3K inhibitor suppressed THP-1 cell differentiation into macrophages and attenuated the AKT phosphorylation activation by PMA and NONO knockdown during PMA-induced differentiation of THP-1 cells into macrophages. These results suggested an important role of NONO in regulating monocyte-macrophage lineage differentiation and this process was mediated, at least partially, through PI3K/AKT signaling pathway.

非pou结构域含八聚体结合蛋白（NONO）是一种多功能核蛋白，在调控细胞核转录和剪接等过程中发挥重要作用。我们的目的是描述NONO对单核-巨噬细胞谱系分化的影响及其潜在机制。通过建立12-肉豆酸酯（PMA）诱导的THP-1细胞分化模型和巨噬细胞集落刺激因子（M-CSF）诱导的小鼠骨髓细胞分化模型，研究了NONO在单核细胞-巨噬细胞谱系分化过程中的表达模式和作用。研究发现，在m - csf诱导小鼠骨髓细胞向巨噬细胞分化和pma诱导THP-1人单核白血病细胞向巨噬细胞分化的过程中，NONO蛋白的表达逐渐降低。Nono基因敲除（Nono K.O.）小鼠骨髓细胞和Nono基因敲除（Nono K.D.）小鼠骨髓细胞单核细胞-巨噬细胞谱系分化过程增强。THP-1细胞。研究还发现，在巨噬细胞谱系分化过程中，NONO表达的降低会增强AKT磷酸化。同时，PI3K抑制剂抑制THP-1细胞向巨噬细胞的分化，减弱PMA诱导THP-1细胞向巨噬细胞分化过程中PMA对AKT磷酸化的激活和NONO的敲除。这些结果表明NONO在调节单核-巨噬细胞谱系分化中起重要作用，并且该过程至少部分通过PI3K/AKT信号通路介导。

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引用次数: 0

Emerging role of alternative splicing in oral and maxillofacial development 选择性剪接在口腔和颌面发育中的新作用

IF 2.6 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2025-08-13 DOI: 10.1016/j.diff.2025.100900

Yinyu Fu, Bo Yang, Ling Lai, Jun He, Xinzhu Li , Jin Hou

The excision of introns and subsequent ligation of exons in precursor messenger RNA (pre-mRNA) is a fundamental mechanism requisite for the expression of eukaryotic genes. Alternative splicing (AS) serves as a potent amplifying factor, augmenting the spectrum of protein isoforms that can emanate from a singular genetic locus, thereby bolstering proteomic diversity. Perturbations in the regulatory framework of pre-mRNA splicing have been associated with an extensive array of pathological conditions. Oral and maxillofacial morphogenesis, a multifaceted process governed by intricate molecular interactions during embryonic development, is also susceptible to the modulating influence of alternative splicing. Aberrations or dysfunctions in the components responsible for alternative splicing during this critical developmental window can culminate in abnormal craniofacial architectures. In this scholarly review, our emphasis is placed on the exploration of RNA splicing as an emergent feature in oral and maxillofacial development. Importantly, we spotlight instances of splicing dysregulation that contribute to either non-syndromic or syndromic manifestations of cleft palate and enamel developmental anomalies. Deepening our understanding of the role of RNA splicing components and potential downstream effectors in oral and maxillofacial development may provide invaluable insights for prenatal diagnostic modalities.

前体信使RNA （pre-mRNA）内含子的切除和随后的外显子连接是真核生物基因表达所必需的基本机制。选择性剪接（AS）作为一种有效的放大因子，增加了从单一遗传位点产生的蛋白质同工型的光谱，从而增强了蛋白质组学的多样性。在前mrna剪接的调控框架的扰动已经与广泛的病理条件阵列相关。口腔和颌面形态发生是一个多方面的过程，受胚胎发育过程中复杂的分子相互作用支配，也容易受到选择性剪接的调节影响。在这个关键的发育窗口期间，负责选择性剪接的组件的畸变或功能障碍可能导致颅面结构异常。在这篇学术综述中，我们的重点放在探索RNA剪接作为口腔和颌面发育的一个新兴特征上。重要的是，我们关注剪接失调的实例，这些实例可能导致腭裂和牙釉质发育异常的非综合征或综合征表现。加深我们对RNA剪接成分和潜在下游效应物在口腔和颌面发育中的作用的理解可能为产前诊断方式提供宝贵的见解。

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引用次数: 0

WNT7A

IF 2.6 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2025-08-07 DOI: 10.1016/j.diff.2025.100899

Naomi M. Calhoun, Richard R. Behringer

WNT7A regulates numerous developmental processes. It can activate canonical and non-canonical signaling depending on context. It is expressed in the developing central nervous system, limb buds, reproductive organs, and other tissues. Spontaneous and targeted Wnt7a mutations in mouse models resulted in abnormal limbs, defects in male and female reproductive tract organs, infertility, and defects in cerebellar axon remodeling. In zebrafish, wnt7aa mutants exhibited neurogenesis and angiogenesis defects in the central nervous system. In humans, recessive WNT7A missense and nonsense mutations resulted in severe limb and pelvic bone defects. Alterations in WNT7A expression correlated with multiple types of cancer.

WNT7A调控许多发育过程。它可以根据上下文激活规范和非规范信号。它在发育中的中枢神经系统、肢体芽、生殖器官和其他组织中表达。小鼠模型中自发和靶向的Wnt7a突变导致四肢异常、雄性和雌性生殖道器官缺陷、不育和小脑轴突重塑缺陷。在斑马鱼中，wnt7aa突变体在中枢神经系统中表现出神经发生和血管生成缺陷。在人类中，隐性WNT7A错义和无义突变导致严重的肢体和骨盆骨缺损。WNT7A表达的改变与多种类型的癌症相关。

引用次数: 0

Roles and mechanisms of piRNAs in self-renewal and differentiation of germline stem cells pirna在生殖系干细胞自我更新和分化中的作用和机制

IF 2.6 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2025-07-25 DOI: 10.1016/j.diff.2025.100897

Jianchun Zhang , Xiexin Wang , Xuanhe Feng , Yan Chen , Ke Yu , Zhiwei Jiang

piRNAs are considered to be plentiful and heterogeneous non-coding RNAs, playing a significant role in embryonic patterning and stem cells. In recent research, scientists have explored how piRNAs contribute to both biological processes and roles in stem cells. Their regulatory action is essential for enabling stem cells to both renew themselves and differentiate into specialized types. piRNAs mediate transposable element (TE) silencing to ensure gene integrity via epigenetic repression mechanisms, ‘ping-pong’ mechanism, and splicing. Recent findings reveal that piRNAs are involved in silencing TE and regulating protein-coding mRNAs. This regulation suppresses the target mRNAs either via cleavage mediated by PIWI proteins or through recruiting the CCR4-NOT complex. Thereby the processes of stem cell self-renewal and differentiation have been lightened. piRNAs together with PIWI proteins contribute to controlling the translation of factors. As biological translation regulators, piRNAs in germline stem cells (GSCs) can trigger cell fate by specific regulation of mRNA targets. This role of piRNAs in regulating translation appears to be conserved across stem cells and is likely essential for maintaining stem cell balance. Furthermore, piRNAs along with PIWI proteins can be the biomarkers of stem cells. This review concentrates on recent findings that explore the developmental and biological functions of piRNAs, with a particular emphasis on their contributions to early embryonic organization and the regulation of stem cell behavior.

pirna被认为是一种丰富且异质性的非编码rna，在胚胎模式和干细胞中起着重要作用。在最近的研究中，科学家们探索了pirna如何促进干细胞的生物学过程和作用。它们的调节作用对于干细胞自我更新和分化为特化类型至关重要。pirna介导转座因子（TE）沉默，通过表观遗传抑制机制、“乒乓”机制和剪接来确保基因完整性。最近的研究结果表明，pirna参与沉默TE和调节蛋白质编码mrna。这种调控通过PIWI蛋白介导的裂解或通过募集CCR4-NOT复合体来抑制靶mrna。因此，干细胞自我更新和分化的过程已经减轻。pirna与PIWI蛋白一起参与控制因子的翻译。作为生物翻译调节剂，生殖系干细胞（GSCs）中的pirna可以通过特异性调控mRNA靶点来触发细胞命运。pirna在调节翻译中的作用似乎在干细胞中是保守的，并且可能是维持干细胞平衡所必需的。此外，pirna和PIWI蛋白可以作为干细胞的生物标志物。本文综述了pirna在发育和生物学功能方面的最新研究成果，特别强调了它们在早期胚胎组织和干细胞行为调控中的作用。

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引用次数: 0

Evaluation of chondrogenesis and osteogenesis in human mesenchymal stem cells, chondrocytes, and chondroprogenitors using molecular markers, cellular markers and polarized microscopy 利用分子标记、细胞标记和极化显微镜评价人间充质干细胞、软骨细胞和软骨祖细胞的软骨形成和成骨

IF 2.6 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2025-07-25 DOI: 10.1016/j.diff.2025.100898

Archa Suresh , Ayshath Ruksana C , Ganesh Parasuraman , Mohana Priya , Grace Rebekah , Christo Jeyaraj , Elizabeth Vinod

Purpose

Fibronectin adhesion assay progenitors (FAA-CPs) and migratory assay progenitors (MCPs), subsets of mesenchymal-like stromal cells (MSCs), exhibit superior in-vitro chondrogenic potential compared to bone marrow (BM)-MSCs and chondrocytes. To assess this potential, differentiation studies followed by confirmatory staining for collagen deposition are utilized. Polarized light microscopy (PLM), based on birefringence principles, is a valuable tool for visualizing organized collagen fibers. Its use as a predictive tool for assessing chondrogenesis and osteogenesis has not been reported.

Methods

This study involved FAA-CPs, MCPs, chondrocytes, and BM-MSCs derived from osteoarthritic knee joints (n = 3). After phenotypic characterization, the cells underwent chondrogenic and osteogenic differentiation, followed by Picrosirius red staining and PLM analysis, including immunohistochemical analysis for collagen types I, II, and X.

Results

Birefringence assessment revealed greater collagen fibril alignment and significant remodeling in the BM-MSC group, which exhibited an arcade-like pattern. The MCP group displayed well-organized collagen fibrils in pericellular zones and as a peripheral band, while chondrocytes and FAA-CPs exhibited lower intensity birefringence, indicating random alignment. Areas with higher collagen type II deposition corresponded to reduced collagen type I and the absence of collagen type X, highlighting the unique fibrillar network seen with PLM was indicative of collagen type II.

Conclusion

While its application for osteogenesis was limited, probably due to the non-fibrillar nature of collagen type X, its value for chondrogenesis is notable. Although not directly reflecting chondrogenesis, PLM can serve as a valuable tool for gaining insights into collagen remodeling, particularly concerning collagen type II during chondrogenic differentiation.

目的：纤连蛋白粘附试验祖细胞（FAA-CPs）和迁移试验祖细胞（MCPs）是间充质样基质细胞（MSCs）的亚群，与骨髓(BM)-MSCs和软骨细胞相比，它们在体外表现出更强的成软骨潜能。为了评估这一潜力，分化研究随后证实染色胶原沉积被利用。偏振光显微镜（PLM），基于双折射原理，是一个有价值的工具，可视化组织胶原纤维。它作为评估软骨形成和成骨形成的预测工具尚未报道。方法本研究涉及骨关节炎膝关节的fa - cps、MCPs、软骨细胞和BM-MSCs （n = 3）。表型鉴定后，细胞进行软骨和成骨分化，随后进行Picrosirius红染色和PLM分析，包括I型、II型和x型胶原的免疫组织化学分析。结果双折射评估显示，BM-MSC组胶原纤维排列更大，重构明显，呈拱廊状。MCP组在细胞周带和外周带中显示组织良好的胶原原纤维，而软骨细胞和fa - cps表现出较低强度的双折射，表明随机排列。II型胶原沉积较多的区域对应于I型胶原减少和X型胶原缺失，突出显示PLM中独特的纤维网络，表明II型胶原。结论X型胶原的非纤原性可能限制了其在成骨方面的应用，但其在软骨形成方面的价值是显著的。虽然PLM不能直接反映软骨形成，但它可以作为一种有价值的工具，用于深入了解胶原重塑，特别是软骨形成分化过程中的II型胶原。

{"title":"Evaluation of chondrogenesis and osteogenesis in human mesenchymal stem cells, chondrocytes, and chondroprogenitors using molecular markers, cellular markers and polarized microscopy","authors":"Archa Suresh , Ayshath Ruksana C , Ganesh Parasuraman , Mohana Priya , Grace Rebekah , Christo Jeyaraj , Elizabeth Vinod","doi":"10.1016/j.diff.2025.100898","DOIUrl":"10.1016/j.diff.2025.100898","url":null,"abstract":"<div><h3>Purpose</h3><div>Fibronectin adhesion assay progenitors (FAA-CPs) and migratory assay progenitors (MCPs), subsets of mesenchymal-like stromal cells (MSCs), exhibit superior in-vitro chondrogenic potential compared to bone marrow (BM)-MSCs and chondrocytes. To assess this potential, differentiation studies followed by confirmatory staining for collagen deposition are utilized. Polarized light microscopy (PLM), based on birefringence principles, is a valuable tool for visualizing organized collagen fibers. Its use as a predictive tool for assessing chondrogenesis and osteogenesis has not been reported.</div></div><div><h3>Methods</h3><div>This study involved FAA-CPs, MCPs, chondrocytes, and BM-MSCs derived from osteoarthritic knee joints (n = 3). After phenotypic characterization, the cells underwent chondrogenic and osteogenic differentiation, followed by Picrosirius red staining and PLM analysis, including immunohistochemical analysis for collagen types I, II, and X.</div></div><div><h3>Results</h3><div>Birefringence assessment revealed greater collagen fibril alignment and significant remodeling in the BM-MSC group, which exhibited an arcade-like pattern. The MCP group displayed well-organized collagen fibrils in pericellular zones and as a peripheral band, while chondrocytes and FAA-CPs exhibited lower intensity birefringence, indicating random alignment. Areas with higher collagen type II deposition corresponded to reduced collagen type I and the absence of collagen type X, highlighting the unique fibrillar network seen with PLM was indicative of collagen type II.</div></div><div><h3>Conclusion</h3><div>While its application for osteogenesis was limited, probably due to the non-fibrillar nature of collagen type X, its value for chondrogenesis is notable. Although not directly reflecting chondrogenesis, PLM can serve as a valuable tool for gaining insights into collagen remodeling, particularly concerning collagen type II during chondrogenic differentiation.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"145 ","pages":"Article 100898"},"PeriodicalIF":2.6,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144722381","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

Mettl3 is required for germline function during Drosophila spermatogenesis 在果蝇精子发生过程中，Mettl3是种系功能所必需的

IF 2.2 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2025-07-13 DOI: 10.1016/j.diff.2025.100895

Alannah Morse, Hailey Kaba, Corinne Leighty, Emily MacLean, Rosemarie Mirabella, Mary Reinaker, Rohan Harris, Jazmyn Moodie, Antonio Rockwell

The m⁶A modification is responsible for regulating several aspects of RNA metabolism. The enzyme that catalyzes this modification Mettl3, is highly conserved and required for numerous biological processes such as spermatogenesis. Here we examine the role of Mettl3 in germline function during Drosophila spermatogenesis. We find that depletion of Mettl3 in the germline results in errors in late-stage spermatogenesis, the process known as spermiogenesis. In germline knockdowns, actin cones bound to spermatids fail to remain tightly packed during the individualization process. Issues with actin cone assembly appear to disrupt progression through spermiogenesis resulting in waste bag deficiency, an indicator of abnormal spermatid individualization. These errors result in little to no sperm in seminal vesicles culminating in reduced fertility in germline knockdowns. Furthermore, our findings suggest Hsp60B is misregulated in knockdowns, which potentially explains at least some observed phenotypes. Collectively, the data presented in this investigation suggests Mettl3 has a prominent role in regulating spermatid differentiation during Drosophila spermatogenesis.

m6A修饰负责调节RNA代谢的几个方面。催化这种修饰的酶Mettl3是高度保守的，是许多生物过程（如精子发生）所必需的。在这里，我们研究了Mettl3在果蝇精子发生过程中生殖系功能中的作用。我们发现生殖系中Mettl3的缺失会导致后期精子发生的错误，这一过程被称为精子发生。在种系基因敲低中，与精子结合的肌动蛋白锥在个体化过程中不能保持紧密的包裹。肌动蛋白锥体组装的问题似乎破坏了精子发生的进程，导致废物袋缺乏，这是精子异常个体化的一个指标。这些错误导致精囊中精子很少甚至没有精子，最终导致生殖细胞敲低导致生育能力降低。此外，我们的研究结果表明Hsp60B在基因敲低中被错误调控，这可能解释了至少一些观察到的表型。总的来说，本研究的数据表明，在果蝇精子发生过程中，Mettl3在调节精细胞分化中起着重要作用。

{"title":"Mettl3 is required for germline function during Drosophila spermatogenesis","authors":"Alannah Morse, Hailey Kaba, Corinne Leighty, Emily MacLean, Rosemarie Mirabella, Mary Reinaker, Rohan Harris, Jazmyn Moodie, Antonio Rockwell","doi":"10.1016/j.diff.2025.100895","DOIUrl":"10.1016/j.diff.2025.100895","url":null,"abstract":"<div><div>The m<sup>6</sup>A modification is responsible for regulating several aspects of RNA metabolism. The enzyme that catalyzes this modification Mettl3, is highly conserved and required for numerous biological processes such as spermatogenesis. Here we examine the role of Mettl3 in germline function during <em>Drosophila</em> spermatogenesis. We find that depletion of Mettl3 in the germline results in errors in late-stage spermatogenesis, the process known as spermiogenesis. In germline knockdowns, actin cones bound to spermatids fail to remain tightly packed during the individualization process. Issues with actin cone assembly appear to disrupt progression through spermiogenesis resulting in waste bag deficiency, an indicator of abnormal spermatid individualization. These errors result in little to no sperm in seminal vesicles culminating in reduced fertility in germline knockdowns. Furthermore, our findings suggest <em>Hsp60B</em> is misregulated in knockdowns, which potentially explains at least some observed phenotypes. Collectively, the data presented in this investigation suggests Mettl3 has a prominent role in regulating spermatid differentiation during <em>Drosophila</em> spermatogenesis.</div></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":"145 ","pages":"Article 100895"},"PeriodicalIF":2.2,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144665708","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

Bdnf and Ntrk2 functions promote but are not essential for spinal cord myelination in larval zebrafish Bdnf和Ntrk2的功能促进了斑马鱼幼体脊髓髓鞘形成，但不是必需的

IF 2.2 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2025-07-12 DOI: 10.1016/j.diff.2025.100896

Kristen Russell , Christina A. Kearns , Macie B. Walker , Christopher S. Knoeckel , Angeles B. Ribera , Caleb A. Doll , Bruce Appel

Myelin, a specialized membrane produced by oligodendroglial cells in the central nervous system, wraps axons to enhance conduction velocity and maintain axon health. Not all axons are myelinated, and not all myelinated axons are uniformly wrapped along their lengths. Several lines of evidence indicate that neuronal activity can influence myelination, however, the cellular and molecular mechanisms that mediate communication between axons and oligodendrocytes remain poorly understood. Prior research showed that the neurotrophic growth factor Bdnf and its receptor Ntrk2 promote myelination in rodents, raising the possibility that Bdnf and Ntrk2 convey myelin-promoting signals from neurons to oligodendrocytes. We explored this possibility using a combination of gene expression analyses, gene function tests, and myelin sheath formation assays in zebrafish larvae. Altogether, our data indicate that, although not essential for myelination, Bdnf-Ntrk2 signaling contributes to the timely formation of myelin in the developing zebrafish spinal cord.

髓磷脂是由中枢神经系统少突胶质细胞产生的一种特殊膜，包裹轴突以提高传导速度，维持轴突健康。并不是所有的轴突都有髓鞘，也不是所有有髓鞘的轴突沿其长度均匀包裹。一些证据表明，神经元活动可以影响髓鞘形成，然而，介导轴突和少突胶质细胞之间通讯的细胞和分子机制仍然知之甚少。先前的研究表明，神经营养生长因子Bdnf及其受体Ntrk2促进啮齿动物的髓鞘形成，这提出了Bdnf和Ntrk2将髓鞘促进信号从神经元传递到少突胶质细胞的可能性。我们通过对斑马鱼幼虫的基因表达分析、基因功能测试和髓鞘形成分析来探索这种可能性。总之，我们的数据表明，尽管Bdnf-Ntrk2信号不是髓鞘形成所必需的，但它有助于发育中的斑马鱼脊髓髓鞘的及时形成。

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引用次数: 0

Corrigendum to “The mechanism of EGF in promoting skeletal muscle post-injury regeneration” [Differentiation 143 (2025) 100862] “EGF促进骨骼肌损伤后再生的机制”的更正[分化143 (2025)100862]

IF 2.2 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2025-07-01 DOI: 10.1016/j.diff.2025.100885

Huaixin Teng , Yongze Liu , Ruotong Hao , Lu Zhang , Xiaoyu Zhang , Shufeng Li , Shuang Li , Huili Tong

引用次数: 0

One Wnt to lead them all: a Wnt1 primer 一个Wnt可以引领所有Wnt：一个Wnt1引物

IF 2.2 3区生物学 Q4 CELL BIOLOGY

Differentiation

Pub Date : 2025-06-24 DOI: 10.1016/j.diff.2025.100884

Arne C. Lekven, Sarah Empie , Richard Saoud

Wnt1 was originally identified by virtue of its mutant phenotype in Drosophila and its causation of mammary tumors in mice, but, in its history, Wnt1 has been a nexus for ground-breaking discoveries in developmental biology, evolutionary biology, and disease. Wnt1 orthologs are found across the animal kingdom and play a role in a multitude of developmental and homeostatic mechanisms involving proliferation, cell fate specification, stem cell maintenance and tissue homeostasis. In vertebrates, Wnt1 is located in a syntenic chromosome neighborhood that is essential to its conserved expression in the developing nervous system. Wnt1 is essential for nervous system development, in particular for the midbrain and anterior hindbrain. Wnt1 also is essential for bone homeostasis, and mutant alleles are behind severe cases of recessive osteogenesis imperfecta in humans. This primer reviews the illustrious history of Wnt1, its gene structure and regulation, expression, loss-of-function consequences, and connection to human disease.

Wnt1最初是由于其在果蝇中的突变表型和在小鼠中引起乳腺肿瘤而被发现的，但是，在其历史上，Wnt1已经成为发育生物学、进化生物学和疾病领域突破性发现的纽带。Wnt1同源基因在动物王国中广泛存在，并在多种发育和体内平衡机制中发挥作用，包括增殖、细胞命运规范、干细胞维持和组织体内平衡。在脊椎动物中，Wnt1位于同染色体附近，这对其在发育中的神经系统中的保守表达至关重要。Wnt1对神经系统发育至关重要，特别是中脑和后脑前部。Wnt1也是骨稳态所必需的，突变等位基因是人类严重隐性成骨不全病例的原因。本引物回顾了Wnt1的辉煌历史、其基因结构和调控、表达、功能丧失后果以及与人类疾病的联系。

引用次数: 0