Pub Date : 2024-11-28eCollection Date: 2025-02-01DOI: 10.1016/j.cellin.2024.100223
Yuxin Du, Yin Shen
Retinal degenerative diseases encompass a diverse range of eye conditions that result in blindness, many due to photoreceptor dysfunction and loss. Regrettably, current clinical treatments are frequently not overly effective. However, photoreceptor transplantation shows promise as a potential therapy for late-stage retinal degenerative diseases. This article will review the various donor cell sources for this transplantation, as well as the mechanisms and factors that impact donor cell integration and material transfer, donor cell maturation, and other auxiliary methods that can be combined with photoreceptor transplantation to treat these degenerative retinal diseases.
{"title":"Progress in photoreceptor replacement therapy for retinal degenerative diseases.","authors":"Yuxin Du, Yin Shen","doi":"10.1016/j.cellin.2024.100223","DOIUrl":"10.1016/j.cellin.2024.100223","url":null,"abstract":"<p><p>Retinal degenerative diseases encompass a diverse range of eye conditions that result in blindness, many due to photoreceptor dysfunction and loss. Regrettably, current clinical treatments are frequently not overly effective. However, photoreceptor transplantation shows promise as a potential therapy for late-stage retinal degenerative diseases. This article will review the various donor cell sources for this transplantation, as well as the mechanisms and factors that impact donor cell integration and material transfer, donor cell maturation, and other auxiliary methods that can be combined with photoreceptor transplantation to treat these degenerative retinal diseases.</p>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 1","pages":"100223"},"PeriodicalIF":0.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-22eCollection Date: 2025-02-01DOI: 10.1016/j.cellin.2024.100224
Chao Chen, Xinjian Li
Itaconate which is discovered as a mammalian metabolite possessing antimicrobial and immunoregulatory activity has attracted much attention in the field of immunometabolism. Itaconate is synthesized by myeloid cells under conditions of pathogen infection and sterile inflammation. In addition to regulating immune response of myeloid cells, itaconate secreted from myeloid cells can also be taken up by non-myeloid cells to exert immunoregulatory effects in a cell non-autonomous manner. In this review, we recap the discovery of itaconate as a distinct immunologic regulator and effector, describe the development of itaconate biosensor, and detail the recent findings that decipher the mechanism underlying intercellular transport of itaconate. Based on these knowledges, we propose itaconate is a messenger transmitting immunologic signals from myeloid cells to other types of cells during host inflammation and immune defense.
{"title":"The cell autonomous and non-autonomous roles of itaconate in immune response.","authors":"Chao Chen, Xinjian Li","doi":"10.1016/j.cellin.2024.100224","DOIUrl":"10.1016/j.cellin.2024.100224","url":null,"abstract":"<p><p>Itaconate which is discovered as a mammalian metabolite possessing antimicrobial and immunoregulatory activity has attracted much attention in the field of immunometabolism. Itaconate is synthesized by myeloid cells under conditions of pathogen infection and sterile inflammation. In addition to regulating immune response of myeloid cells, itaconate secreted from myeloid cells can also be taken up by non-myeloid cells to exert immunoregulatory effects in a cell non-autonomous manner. In this review, we recap the discovery of itaconate as a distinct immunologic regulator and effector, describe the development of itaconate biosensor, and detail the recent findings that decipher the mechanism underlying intercellular transport of itaconate. Based on these knowledges, we propose itaconate is a messenger transmitting immunologic signals from myeloid cells to other types of cells during host inflammation and immune defense.</p>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 1","pages":"100224"},"PeriodicalIF":0.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-12DOI: 10.1016/j.cellin.2024.100213
Xin Li , Chengzhi Liu , Zhichao Lei , Huan Chen , Liang Wang
Eukaryotic genomes are organized into distinct chromatin compartments, some of which exhibit properties of biomolecular condensates. These condensates primarily form due to chromatin-associated proteins/complexes (CAPs). CAPs play a crucial role in gene expression, functioning as either transcriptional repressors or activators. Phase separation, a well-established biophysical phenomenon, is a key driver of chromatin condensate formation by CAPs. Notably, multivalent CAPs with the ability to engage in diverse interactions promote chromatin compaction, leading to the formation of transcriptionally repressed compartments. Conversely, interactions between intrinsically disordered region (IDR)-containing transcriptional regulators, mediated by their multivalent IDRs, lead to the formation of protein-rich, transcriptionally active droplets on decondensed genomic regions. Interestingly, both repressive heterochromatin and activating euchromatin condensates exhibit spontaneous phase separation and selectively enrich components with concordant transcriptional functions. This review delves into the mechanisms by which transcriptionally repressive CAPs orchestrate the formation of repressed chromatin domains. We further explore how a diverse array of transcription-related CAPs or core histone variants, via phase separation, influence gene expression by inducing erroneous transcription events, regulating expression levels, and facilitating the interconversion of transcriptionally repressed and active regions.
真核生物基因组被组织成不同的染色质区室，其中一些表现出生物分子凝聚物的特性。这些凝聚体主要是由染色质相关蛋白/复合物（CAPs）形成的。CAPs 在基因表达中起着至关重要的作用，可作为转录抑制因子或激活因子发挥作用。相分离是一种公认的生物物理现象，是 CAPs 形成染色质凝聚物的关键驱动因素。值得注意的是，能够参与多种相互作用的多价 CAP 可促进染色质的压实，从而形成转录抑制区。与此相反，含有内在紊乱区（IDR）的转录调节因子在多价 IDR 的介导下相互作用，导致在解聚的基因组区域形成富含蛋白质、转录活跃的液滴。有趣的是，抑制性异染色质和激活性超染色质凝集物都表现出自发的相分离，并选择性地富集具有一致转录功能的成分。本综述深入探讨了转录抑制性 CAP 协调形成抑制性染色质域的机制。我们将进一步探讨各种与转录相关的 CAP 或核心组蛋白变体如何通过相分离，诱导错误的转录事件、调节表达水平以及促进转录抑制区和活性区的相互转换，从而影响基因表达。
{"title":"Phase-separated chromatin compartments: Orchestrating gene expression through condensation","authors":"Xin Li , Chengzhi Liu , Zhichao Lei , Huan Chen , Liang Wang","doi":"10.1016/j.cellin.2024.100213","DOIUrl":"10.1016/j.cellin.2024.100213","url":null,"abstract":"<div><div>Eukaryotic genomes are organized into distinct chromatin compartments, some of which exhibit properties of biomolecular condensates. These condensates primarily form due to chromatin-associated proteins/complexes (CAPs). CAPs play a crucial role in gene expression, functioning as either transcriptional repressors or activators. Phase separation, a well-established biophysical phenomenon, is a key driver of chromatin condensate formation by CAPs. Notably, multivalent CAPs with the ability to engage in diverse interactions promote chromatin compaction, leading to the formation of transcriptionally repressed compartments. Conversely, interactions between intrinsically disordered region (IDR)-containing transcriptional regulators, mediated by their multivalent IDRs, lead to the formation of protein-rich, transcriptionally active droplets on decondensed genomic regions. Interestingly, both repressive heterochromatin and activating euchromatin condensates exhibit spontaneous phase separation and selectively enrich components with concordant transcriptional functions. This review delves into the mechanisms by which transcriptionally repressive CAPs orchestrate the formation of repressed chromatin domains. We further explore how a diverse array of transcription-related CAPs or core histone variants, via phase separation, influence gene expression by inducing erroneous transcription events, regulating expression levels, and facilitating the interconversion of transcriptionally repressed and active regions.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"3 6","pages":"Article 100213"},"PeriodicalIF":0.0,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142532224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-11DOI: 10.1016/j.cellin.2024.100212
Chen Zhao , Liang Wang , Junbao Wang, Kuan Tian, Xiaojiao Hua, Fangyu Wang, Yan Zhou
{"title":"Transcripts derived from the neocortical enhancer of Ctnnb1 promote the enhancer-promoter interaction and maintain Ctnnb1 transcription","authors":"Chen Zhao , Liang Wang , Junbao Wang, Kuan Tian, Xiaojiao Hua, Fangyu Wang, Yan Zhou","doi":"10.1016/j.cellin.2024.100212","DOIUrl":"10.1016/j.cellin.2024.100212","url":null,"abstract":"","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 1","pages":"Article 100212"},"PeriodicalIF":0.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142651970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-11DOI: 10.1016/j.cellin.2024.100210
Yong Wang , Xinping Liu , Zheng Liu , Shasha Hua , Kai Jiang
Tumor suppressor protein Adenomatous polyposis coli protein (APC) is an EB-binding and microtubule (MT) plus end-tracking protein; however, how exactly APC regulates MT dynamics remains elusive. Here, we show that in LLC-PK1 cells, APC and KIF2A, an MT depolymerase, form a complex clustering at the cell edge and destabilize MTs at the MT plus ends. Further biochemical characterization and mutational analysis reveal key residues for the APC-KIF2A interaction. In addition, APC counteracts the major MT-stabilizer CLASPs at MT plus ends and promotes directional cell migration via modulating cell adhesion force. Reconstitution experiments demonstrate that APC potentiates KIF2A-induced MT catastrophes and antagonizes the stabilizing effect of CLASP2 in vitro. In summary, APC functions as a positive regulator of MT-destabilizer and a negative regulator of MT-stabilizer to orchestrate MT dynamics.
{"title":"APC orchestrates microtubule dynamics by acting as a positive regulator of KIF2A and a negative regulator of CLASPs","authors":"Yong Wang , Xinping Liu , Zheng Liu , Shasha Hua , Kai Jiang","doi":"10.1016/j.cellin.2024.100210","DOIUrl":"10.1016/j.cellin.2024.100210","url":null,"abstract":"<div><div>Tumor suppressor protein Adenomatous polyposis coli protein (APC) is an EB-binding and microtubule (MT) plus end-tracking protein; however, how exactly APC regulates MT dynamics remains elusive. Here, we show that in LLC-PK1 cells, APC and KIF2A, an MT depolymerase, form a complex clustering at the cell edge and destabilize MTs at the MT plus ends. Further biochemical characterization and mutational analysis reveal key residues for the APC-KIF2A interaction. In addition, APC counteracts the major MT-stabilizer CLASPs at MT plus ends and promotes directional cell migration via modulating cell adhesion force. Reconstitution experiments demonstrate that APC potentiates KIF2A-induced MT catastrophes and antagonizes the stabilizing effect of CLASP2 <em>in vitro</em>. In summary, APC functions as a positive regulator of MT-destabilizer and a negative regulator of MT-stabilizer to orchestrate MT dynamics.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 1","pages":"Article 100210"},"PeriodicalIF":0.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142704837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1016/j.cellin.2024.100214
Katherine N. Degner , Jessica L. Bell , Sean D. Jones , Hyejung Won
The human genome is largely noncoding, yet the field is still grasping to understand how noncoding variants impact transcription and contribute to disease etiology. The massively parallel reporter assay (MPRA) has been employed to characterize the function of noncoding variants at unprecedented scales, but its application has been largely limited by the in vitro context. The field will benefit from establishing a systemic platform to study noncoding variant function across multiple tissue types under physiologically relevant conditions. However, to date, MPRA has been applied to only a handful of in vivo conditions. Given the complexity of the central nervous system and its widespread interactions with all other organ systems, our understanding of neuropsychiatric disorder-associated noncoding variants would be greatly advanced by studying their functional impact in the intact brain. In this review, we discuss the importance, technical considerations, and future applications of implementing MPRA in the in vivo space with the focus on neuropsychiatric disorders.
{"title":"Just a SNP away: The future of in vivo massively parallel reporter assay","authors":"Katherine N. Degner , Jessica L. Bell , Sean D. Jones , Hyejung Won","doi":"10.1016/j.cellin.2024.100214","DOIUrl":"10.1016/j.cellin.2024.100214","url":null,"abstract":"<div><div>The human genome is largely noncoding, yet the field is still grasping to understand how noncoding variants impact transcription and contribute to disease etiology. The massively parallel reporter assay (MPRA) has been employed to characterize the function of noncoding variants at unprecedented scales, but its application has been largely limited by the <em>in vitro</em> context. The field will benefit from establishing a systemic platform to study noncoding variant function across multiple tissue types under physiologically relevant conditions. However, to date, MPRA has been applied to only a handful of <em>in vivo</em> conditions. Given the complexity of the central nervous system and its widespread interactions with all other organ systems, our understanding of neuropsychiatric disorder-associated noncoding variants would be greatly advanced by studying their functional impact in the intact brain. In this review, we discuss the importance, technical considerations, and future applications of implementing MPRA in the <em>in vivo</em> space with the focus on neuropsychiatric disorders.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 1","pages":"Article 100214"},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142651969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 10.1016/j.cellin.2024.100211
Qiu Pan , Xiao-Lian Zhang
Core fucosylation, catalyzed by α1,6-fucosyltransferase (FUT8), is an important N-glycosylation modification process that attaches a fucose residue via an α1,6-linkage to the core N-acetylglucosamine of N-glycans in mammals. Research over the past three decades has revealed the critical role of FUT8-mediated core fucosylation modification in various physiological and pathological processes, including cell growth, adhesion, receptor activation, antibody-dependent cellular cytotoxicity (ADCC), tumor metastasis and infections. This review discusses the immune system function involving FUT8 and the mechanisms by which core fucosylation regulates immunity and contributes to disease. A deeper understanding of these mechanisms can provide insights into cellular biology and suggest new therapeutic approaches and targets for related diseases.
{"title":"Roles of core fucosylation modification in immune system and diseases","authors":"Qiu Pan , Xiao-Lian Zhang","doi":"10.1016/j.cellin.2024.100211","DOIUrl":"10.1016/j.cellin.2024.100211","url":null,"abstract":"<div><div>Core fucosylation, catalyzed by α1,6-fucosyltransferase (FUT8), is an important <em>N-</em>glycosylation modification process that attaches a fucose residue via an α1,6-linkage to the core <em>N</em>-acetylglucosamine of <em>N</em>-glycans in mammals. Research over the past three decades has revealed the critical role of FUT8-mediated core fucosylation modification in various physiological and pathological processes, including cell growth, adhesion, receptor activation, antibody-dependent cellular cytotoxicity (ADCC), tumor metastasis and infections. This review discusses the immune system function involving FUT8 and the mechanisms by which core fucosylation regulates immunity and contributes to disease. A deeper understanding of these mechanisms can provide insights into cellular biology and suggest new therapeutic approaches and targets for related diseases.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 1","pages":"Article 100211"},"PeriodicalIF":0.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142651844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-26DOI: 10.1016/j.cellin.2024.100209
Ke-Jing Li , Lei Qi , Ying-Xuan Zhu , Min He , Qian Xiang , Dao-Qiong Zheng
While genomic alterations are fundamental to biological evolution, enabling adaptation and diversity, they can also result in detrimental outcomes, such as the development of genetic diseases including cancer. The budding yeast Saccharomyces cerevisiae serves as an exemplary model for investigating the mechanisms behind various genomic alterations, including point mutations, chromosomal rearrangements, and whole-chromosome aneuploidy. In this review, we highlight the application of genetic screening systems to assess the mutagenic effects of physical and chemical agents efficiently. Additionally, we discuss the utilization of high-throughput sequencing technologies to uncover comprehensive genomic alterations and rare genetic events. We provide a detailed summary of the features of genomic alterations and discuss the genetic mechanisms driving these changes under both spontaneous and stress-induced conditions. Given the high conservation of DNA replication and repair machinery across different organisms, the insights gained from studies on yeast offer valuable perspectives for understanding the delicate balance between genome plasticity and integrity in other species.
虽然基因组改变是生物进化的基础，能促进生物的适应性和多样性，但它们也可能导致有害的结果，如发展成包括癌症在内的遗传疾病。芽殖酵母是研究点突变、染色体重排和全染色体非整倍体等各种基因组改变背后机制的典范。在这篇综述中，我们重点介绍了基因筛选系统在有效评估物理和化学试剂诱变效应方面的应用。此外，我们还讨论了如何利用高通量测序技术来发现全面的基因组改变和罕见遗传事件。我们详细总结了基因组改变的特征，并讨论了在自发和应激诱导条件下驱动这些改变的遗传机制。鉴于不同生物的 DNA 复制和修复机制高度一致，从酵母研究中获得的见解为理解其他物种基因组可塑性和完整性之间的微妙平衡提供了宝贵的视角。
{"title":"Spontaneous and environment induced genomic alterations in yeast model","authors":"Ke-Jing Li , Lei Qi , Ying-Xuan Zhu , Min He , Qian Xiang , Dao-Qiong Zheng","doi":"10.1016/j.cellin.2024.100209","DOIUrl":"10.1016/j.cellin.2024.100209","url":null,"abstract":"<div><div>While genomic alterations are fundamental to biological evolution, enabling adaptation and diversity, they can also result in detrimental outcomes, such as the development of genetic diseases including cancer. The budding yeast <em>Saccharomyces cerevisiae</em> serves as an exemplary model for investigating the mechanisms behind various genomic alterations, including point mutations, chromosomal rearrangements, and whole-chromosome aneuploidy. In this review, we highlight the application of genetic screening systems to assess the mutagenic effects of physical and chemical agents efficiently. Additionally, we discuss the utilization of high-throughput sequencing technologies to uncover comprehensive genomic alterations and rare genetic events. We provide a detailed summary of the features of genomic alterations and discuss the genetic mechanisms driving these changes under both spontaneous and stress-induced conditions. Given the high conservation of DNA replication and repair machinery across different organisms, the insights gained from studies on yeast offer valuable perspectives for understanding the delicate balance between genome plasticity and integrity in other species.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 1","pages":"Article 100209"},"PeriodicalIF":0.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142705407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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