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SeqVerify: An accessible analysis tool for cell line genomic integrity, contamination, and gene editing outcomes. SeqVerify:细胞系基因组完整性、污染和基因编辑结果的便捷分析工具。
IF 5.9 2区 医学
Stem Cell Reports Pub Date : 2024-10-08 Epub Date: 2024-09-12 DOI: 10.1016/j.stemcr.2024.08.004
Merrick Pierson Smela, Valerio Pepe, Steven Lubbe, Evangelos Kiskinis, George M Church
{"title":"SeqVerify: An accessible analysis tool for cell line genomic integrity, contamination, and gene editing outcomes.","authors":"Merrick Pierson Smela, Valerio Pepe, Steven Lubbe, Evangelos Kiskinis, George M Church","doi":"10.1016/j.stemcr.2024.08.004","DOIUrl":"10.1016/j.stemcr.2024.08.004","url":null,"abstract":"<p><p>Over the last decade, advances in genome editing and pluripotent stem cell (PSC) culture have let researchers generate edited PSC lines to study a wide variety of biological questions. However, abnormalities in cell lines such as aneuploidy, mutations, on-target and off-target editing errors, and microbial contamination can arise during PSC culture or due to undesired editing outcomes. The ongoing decline of next-generation sequencing prices has made whole-genome sequencing (WGS) a promising option for detecting these abnormalities. However, this approach has been held back by a lack of easily usable data analysis software. Here, we present SeqVerify, a computational pipeline designed to take raw WGS data and a list of intended genome edits, and verify that the edits are present and that there are no abnormalities. We anticipate that SeqVerify will be a useful tool for researchers generating edited PSCs, and more broadly, for cell line quality control in general.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142295963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dynamic spatiotemporal activation of a pervasive neurogenic competence in striatal astrocytes supports continuous neurogenesis following injury. 纹状体星形胶质细胞中普遍存在的神经源能力在时空上的动态激活支持损伤后的持续神经发生。
IF 5.9 2区 医学
Stem Cell Reports Pub Date : 2024-10-08 Epub Date: 2024-09-19 DOI: 10.1016/j.stemcr.2024.08.006
Marco Fogli, Giulia Nato, Philip Greulich, Jacopo Pinto, Marta Ribodino, Gregorio Valsania, Paolo Peretto, Annalisa Buffo, Federico Luzzati
{"title":"Dynamic spatiotemporal activation of a pervasive neurogenic competence in striatal astrocytes supports continuous neurogenesis following injury.","authors":"Marco Fogli, Giulia Nato, Philip Greulich, Jacopo Pinto, Marta Ribodino, Gregorio Valsania, Paolo Peretto, Annalisa Buffo, Federico Luzzati","doi":"10.1016/j.stemcr.2024.08.006","DOIUrl":"10.1016/j.stemcr.2024.08.006","url":null,"abstract":"<p><p>Adult neural stem cells (NSCs) are conventionally regarded as rare cells restricted to two niches: the subventricular zone (SVZ) and the subgranular zone. Parenchymal astrocytes (ASs) can also contribute to neurogenesis after injury; however, the prevalence, distribution, and behavior of these latent NSCs remained elusive. To tackle these issues, we reconstructed the spatiotemporal pattern of striatal (STR) AS neurogenic activation after excitotoxic lesion in mice. Our results indicate that neurogenic potential is widespread among STR ASs but is focally activated at the lesion border, where it associates with different reactive AS subtypes. In this region, similarly to canonical niches, steady-state neurogenesis is ensured by the continuous stochastic activation of local ASs. Activated ASs quickly return to quiescence, while their progeny transiently expand following a stochastic behavior that features an acceleration in differentiation propensity. Notably, STR AS activation rate matches that of SVZ ASs indicating a comparable prevalence of NSC potential.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142295960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Interleukin-1β induces trained innate immunity in human hematopoietic progenitor cells in vitro. 白细胞介素-1β可诱导体外人类造血祖细胞产生训练有素的先天性免疫。
IF 5.9 2区 医学
Stem Cell Reports Pub Date : 2024-09-25 DOI: 10.1016/j.stemcr.2024.09.004
Daniela Flores-Gomez, Willemijn Hobo, Diede van Ens, Elise L Kessler, Boris Novakovic, Nicolaas P M Schaap, Wim H C Rijnen, Leo A B Joosten, Mihai G Netea, Niels P Riksen, Siroon Bekkering
{"title":"Interleukin-1β induces trained innate immunity in human hematopoietic progenitor cells in vitro.","authors":"Daniela Flores-Gomez, Willemijn Hobo, Diede van Ens, Elise L Kessler, Boris Novakovic, Nicolaas P M Schaap, Wim H C Rijnen, Leo A B Joosten, Mihai G Netea, Niels P Riksen, Siroon Bekkering","doi":"10.1016/j.stemcr.2024.09.004","DOIUrl":"https://doi.org/10.1016/j.stemcr.2024.09.004","url":null,"abstract":"<p><p>Innate immune cells can develop a long-lasting hyperresponsive phenotype, termed trained immunity, mediated by epigenetic and metabolic reprogramming. In mice, exposure to Bacille Calmette-Guérin (BCG), β-glucan, or Western diet induces trained immunity by reprogramming hematopoietic progenitor cells (HPCs), through interleukin-1β (IL-1β) signaling in the bone marrow (BM). We investigated whether IL-1β induces trained immunity in primary human BM-derived HPCs in vitro. We exposed human BM-derived HPCs to IL-1β for 4 h. HPCs were expanded and differentiated into monocytes followed by functional and transcriptomic characterization. IL-1β-exposed HPCs showed higher granulocyte-macrophage colony-forming units. The monocyte offspring produced more tumor necrosis factor (TNF) and IL-1β after restimulation with lipopolysaccharide (LPS) and Pam3Cys and is metabolically more active. Transcriptomic analysis showed upregulation of key atherogenic and inflammatory pathways. In conclusion, brief exposure of human BM-derived HPCs to IL-1β in vitro induces a trained immunity phenotype.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Medium acidosis drives cardiac differentiation during mesendoderm cell fate specification from human pluripotent stem cells. 在人类多能干细胞的中胚层细胞命运分化过程中,培养基酸中毒驱动了心脏分化。
IF 5.9 2区 医学
Stem Cell Reports Pub Date : 2024-09-10 Epub Date: 2024-08-22 DOI: 10.1016/j.stemcr.2024.07.012
Weiwei Liu, Hsun-Ting Hsieh, Ziqing He, Xia Xiao, Chengcheng Song, En Xin Lee, Ji Dong, Chon Lok Lei, Jiaxian Wang, Guokai Chen
{"title":"Medium acidosis drives cardiac differentiation during mesendoderm cell fate specification from human pluripotent stem cells.","authors":"Weiwei Liu, Hsun-Ting Hsieh, Ziqing He, Xia Xiao, Chengcheng Song, En Xin Lee, Ji Dong, Chon Lok Lei, Jiaxian Wang, Guokai Chen","doi":"10.1016/j.stemcr.2024.07.012","DOIUrl":"10.1016/j.stemcr.2024.07.012","url":null,"abstract":"<p><p>Effective lineage-specific differentiation is essential to fulfilling the great potentials of human pluripotent stem cells (hPSCs). In this report, we investigate how modulation of medium pH and associated metabolic changes influence mesendoderm differentiation from hPSCs. We show that daily medium pH fluctuations are critical for the heterogeneity of cell fates in the absence of exogenous inducers. Acidic environment alone leads to cardiomyocyte generation without other signaling modulators. In contrast, medium alkalinization is inhibitory to cardiac fate even in the presence of classic cardiac inducers. We then demonstrate that acidic environment suppresses glycolysis to facilitate cardiac differentiation, while alkaline condition promotes glycolysis and diverts the differentiation toward other cell types. We further show that glycolysis inhibition or AMPK activation can rescue cardiac differentiation under alkalinization, and glycolysis inhibition alone can drive cardiac cell fate. This study highlights that pH changes remodel metabolic patterns and modulate signaling pathways to control cell fate.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
mTORC1 mediates the expansion of hematopoietic stem and progenitor cells through ribosome biogenesis protein Urb2 in zebrafish. 在斑马鱼体内,mTORC1 通过核糖体生物生成蛋白 Urb2 介导造血干细胞和祖细胞的扩增。
IF 5.9 2区 医学
Stem Cell Reports Pub Date : 2024-09-10 Epub Date: 2024-08-22 DOI: 10.1016/j.stemcr.2024.07.011
Wenming Huang, Yu Yue, Weifeng Hao, Zhenan Zhang, Pengcheng Cai, Deqin Yang
{"title":"mTORC1 mediates the expansion of hematopoietic stem and progenitor cells through ribosome biogenesis protein Urb2 in zebrafish.","authors":"Wenming Huang, Yu Yue, Weifeng Hao, Zhenan Zhang, Pengcheng Cai, Deqin Yang","doi":"10.1016/j.stemcr.2024.07.011","DOIUrl":"10.1016/j.stemcr.2024.07.011","url":null,"abstract":"<p><p>Mammalian target of rapamycin (mTOR) serves as the key sensor to control protein synthesis, cell growth, and survival. Despite mTOR is reported to regulate hematopoietic stem and progenitor cell (HSPC) engraftment and multiple-lineage hematopoiesis in mice, the roles of unique mTOR complexes (mTORCs) in early HSPC development and HSPC pool formation have not been adequately elucidated. Here, we uncover that mTORC1 is essential for early HSPC expansion in zebrafish. mTORC1 signaling was highly activated in definitive HSPCs during the emerging and expanding stages. Pharmacological or genetic inactivation of mTORC1 would cause defective HSPC expansion and migration due to disrupted cell proliferation. Interestingly, mTORC2 is dispensable for early HSPC development. Ribosome biogenesis protein Urb2 was downregulated upon mTORC1 inhibition, and urb2 overexpression partially rescued the hematopoietic defects in mTORC1-deficient embryos. These data demonstrate that mTORC1 signaling regulates early HSPC expansion through Urb2, and this work will deepen our understanding of mTOR in different physiological processes.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficient generation of human immune system rats using human CD34+ cells. 利用人体 CD34+ 细胞高效生成人体免疫系统大鼠。
IF 5.9 2区 医学
Stem Cell Reports Pub Date : 2024-09-10 Epub Date: 2024-08-15 DOI: 10.1016/j.stemcr.2024.07.005
Séverine Ménoret, Florence Renart-Depontieu, Gaelle Martin, Kader Thiam, Ignacio Anegon
{"title":"Efficient generation of human immune system rats using human CD34<sup>+</sup> cells.","authors":"Séverine Ménoret, Florence Renart-Depontieu, Gaelle Martin, Kader Thiam, Ignacio Anegon","doi":"10.1016/j.stemcr.2024.07.005","DOIUrl":"10.1016/j.stemcr.2024.07.005","url":null,"abstract":"<p><p>Human immune system (HIS) mice generated using human CD34<sup>+</sup> hematopoietic stem cells serve as a pivotal model for the in vivo evaluation of immunotherapies for humans. Yet, HIS mice possess certain limitations. Rats, due to their size and comprehensive immune system, hold promise for translational experiments. Here, we describe an efficacious method for long-term immune humanization, through intrahepatic injection of hCD34<sup>+</sup> cells in newborn immunodeficient rats expressing human SIRPα. In contrast to HIS mice and similar to humans, HIS rats showed in blood a predominance of T cells, followed by B cells. Immune humanization was also high in central and secondary lymphoid organs. HIS rats treated with the anti-human CD3 antibody were depleted of human T cells, and human cytokines were detected in sera. We describe for the first time a method to efficiently generate HIS rats. HIS rats have the potential to be a useful model for translational immunology.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dissecting the impact of differentiation stage, replicative history, and cell type composition on epigenetic clocks. 剖析分化阶段、复制历史和细胞类型组成对表观遗传时钟的影响。
IF 5.9 2区 医学
Stem Cell Reports Pub Date : 2024-09-10 Epub Date: 2024-08-22 DOI: 10.1016/j.stemcr.2024.07.009
Rebecca Gorelov, Aaron Weiner, Aaron Huebner, Masaki Yagi, Amin Haghani, Robert Brooke, Steve Horvath, Konrad Hochedlinger
{"title":"Dissecting the impact of differentiation stage, replicative history, and cell type composition on epigenetic clocks.","authors":"Rebecca Gorelov, Aaron Weiner, Aaron Huebner, Masaki Yagi, Amin Haghani, Robert Brooke, Steve Horvath, Konrad Hochedlinger","doi":"10.1016/j.stemcr.2024.07.009","DOIUrl":"10.1016/j.stemcr.2024.07.009","url":null,"abstract":"<p><p>Epigenetic clocks, built on DNA methylation patterns of bulk tissues, are powerful age predictors, but their biological basis remains incompletely understood. Here, we conducted a comparative analysis of epigenetic age in murine muscle, epithelial, and blood cell types across lifespan. Strikingly, our results show that cellular subpopulations within these tissues, including adult stem and progenitor cells as well as their differentiated progeny, exhibit different epigenetic ages. Accordingly, we experimentally demonstrate that clocks can be skewed by age-associated changes in tissue composition. Mechanistically, we provide evidence that the observed variation in epigenetic age among adult stem cells correlates with their proliferative state, and, fittingly, forced proliferation of stem cells leads to increases in epigenetic age. Collectively, our analyses elucidate the impact of cell type composition, differentiation state, and replicative potential on epigenetic age, which has implications for the interpretation of existing clocks and should inform the development of more sensitive clocks.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cross-site reproducibility of human cortical organoids reveals consistent cell type composition and architecture. 人体皮质器官组织的跨部位可重复性揭示了一致的细胞类型组成和结构。
IF 5.9 2区 医学
Stem Cell Reports Pub Date : 2024-09-10 Epub Date: 2024-08-22 DOI: 10.1016/j.stemcr.2024.07.008
Madison R Glass, Elisa A Waxman, Satoshi Yamashita, Michael Lafferty, Alvaro A Beltran, Tala Farah, Niyanta K Patel, Rubal Singla, Nana Matoba, Sara Ahmed, Mary Srivastava, Emma Drake, Liam T Davis, Meghana Yeturi, Kexin Sun, Michael I Love, Kazue Hashimoto-Torii, Deborah L French, Jason L Stein
{"title":"Cross-site reproducibility of human cortical organoids reveals consistent cell type composition and architecture.","authors":"Madison R Glass, Elisa A Waxman, Satoshi Yamashita, Michael Lafferty, Alvaro A Beltran, Tala Farah, Niyanta K Patel, Rubal Singla, Nana Matoba, Sara Ahmed, Mary Srivastava, Emma Drake, Liam T Davis, Meghana Yeturi, Kexin Sun, Michael I Love, Kazue Hashimoto-Torii, Deborah L French, Jason L Stein","doi":"10.1016/j.stemcr.2024.07.008","DOIUrl":"10.1016/j.stemcr.2024.07.008","url":null,"abstract":"<p><p>While guided human cortical organoid (hCO) protocols reproducibly generate cortical cell types at one site, variability in hCO phenotypes across sites using a harmonized protocol has not yet been evaluated. To determine the cross-site reproducibility of hCO differentiation, three independent research groups assayed hCOs in multiple differentiation replicates from one induced pluripotent stem cell (iPSC) line using a harmonized miniaturized spinning bioreactor protocol across 3 months. hCOs were mostly cortical progenitor and neuronal cell types in reproducible proportions that were consistently organized in cortical wall-like buds. Cross-site differences were detected in hCO size and expression of metabolism and cellular stress genes. Variability in hCO phenotypes correlated with stem cell gene expression prior to differentiation and technical factors associated with seeding, suggesting iPSC quality and treatment are important for differentiation outcomes. Cross-site reproducibility of hCO cell type proportions and organization encourages future prospective meta-analytic studies modeling neurodevelopmental disorders in hCOs.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Individual variation in the emergence of anterior-to-posterior neural fates from human pluripotent stem cells. 人类多能干细胞出现从前向后神经命运的个体差异。
IF 5.9 2区 医学
Stem Cell Reports Pub Date : 2024-09-10 Epub Date: 2024-08-15 DOI: 10.1016/j.stemcr.2024.07.004
Suel-Kee Kim, Seungmae Seo, Genevieve Stein-O'Brien, Amritha Jaishankar, Kazuya Ogawa, Nicola Micali, Victor Luria, Amir Karger, Yanhong Wang, Hyojin Kim, Thomas M Hyde, Joel E Kleinman, Ty Voss, Elana J Fertig, Joo-Heon Shin, Roland Bürli, Alan J Cross, Nicholas J Brandon, Daniel R Weinberger, Joshua G Chenoweth, Daniel J Hoeppner, Nenad Sestan, Carlo Colantuoni, Ronald D McKay
{"title":"Individual variation in the emergence of anterior-to-posterior neural fates from human pluripotent stem cells.","authors":"Suel-Kee Kim, Seungmae Seo, Genevieve Stein-O'Brien, Amritha Jaishankar, Kazuya Ogawa, Nicola Micali, Victor Luria, Amir Karger, Yanhong Wang, Hyojin Kim, Thomas M Hyde, Joel E Kleinman, Ty Voss, Elana J Fertig, Joo-Heon Shin, Roland Bürli, Alan J Cross, Nicholas J Brandon, Daniel R Weinberger, Joshua G Chenoweth, Daniel J Hoeppner, Nenad Sestan, Carlo Colantuoni, Ronald D McKay","doi":"10.1016/j.stemcr.2024.07.004","DOIUrl":"10.1016/j.stemcr.2024.07.004","url":null,"abstract":"<p><p>Variability between human pluripotent stem cell (hPSC) lines remains a challenge and opportunity in biomedicine. In this study, hPSC lines from multiple donors were differentiated toward neuroectoderm and mesendoderm lineages. We revealed dynamic transcriptomic patterns that delineate the emergence of these lineages, which were conserved across lines, along with individual line-specific transcriptional signatures that were invariant throughout differentiation. These transcriptomic signatures predicted an antagonism between SOX21-driven forebrain fates and retinoic acid-induced hindbrain fates. Replicate lines and paired adult tissue demonstrated the stability of these line-specific transcriptomic traits. We show that this transcriptomic variation in lineage bias had both genetic and epigenetic origins, aligned with the anterior-to-posterior structure of early mammalian development, and was present across a large collection of hPSC lines. These findings contribute to developing systematic analyses of PSCs to define the origin and consequences of variation in the early events orchestrating individual human development.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tropomyosin 1 deficiency facilitates cell state transitions and enhances hemogenic endothelial cell specification during hematopoiesis. 在造血过程中,肌球蛋白 1 缺乏会促进细胞状态的转变,并增强造血内皮细胞的分化。
IF 5.9 2区 医学
Stem Cell Reports Pub Date : 2024-09-10 Epub Date: 2024-08-29 DOI: 10.1016/j.stemcr.2024.08.001
Madison B Wilken, Gennadiy Fonar, Rong Qiu, Laura Bennett, Joanna Tober, Catriana Nations, Giulia Pavani, Victor Tsao, James Garifallou, Chayanne Petit, Jean Ann Maguire, Alyssa Gagne, Nkemdilim Okoli, Paul Gadue, Stella T Chou, Deborah L French, Nancy A Speck, Christopher S Thom
{"title":"Tropomyosin 1 deficiency facilitates cell state transitions and enhances hemogenic endothelial cell specification during hematopoiesis.","authors":"Madison B Wilken, Gennadiy Fonar, Rong Qiu, Laura Bennett, Joanna Tober, Catriana Nations, Giulia Pavani, Victor Tsao, James Garifallou, Chayanne Petit, Jean Ann Maguire, Alyssa Gagne, Nkemdilim Okoli, Paul Gadue, Stella T Chou, Deborah L French, Nancy A Speck, Christopher S Thom","doi":"10.1016/j.stemcr.2024.08.001","DOIUrl":"10.1016/j.stemcr.2024.08.001","url":null,"abstract":"<p><p>Tropomyosins coat actin filaments to impact actin-related signaling and cell morphogenesis. Genome-wide association studies have linked Tropomyosin 1 (TPM1) with human blood trait variation. TPM1 has been shown to regulate blood cell formation in vitro, but it remains unclear how or when TPM1 affects hematopoiesis. Using gene-edited induced pluripotent stem cell (iPSC) model systems, we found that TPM1 knockout augmented developmental cell state transitions and key signaling pathways, including tumor necrosis factor alpha (TNF-α) signaling, to promote hemogenic endothelial (HE) cell specification and hematopoietic progenitor cell (HPC) production. Single-cell analyses revealed decreased TPM1 expression during human HE specification, suggesting that TPM1 regulated in vivo hematopoiesis via similar mechanisms. Analyses of a TPM1 gene trap mouse model showed that TPM1 deficiency enhanced HE formation during embryogenesis, without increasing the number of hematopoietic stem cells. These findings illuminate novel effects of TPM1 on developmental hematopoiesis.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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