Pub Date : 2024-11-07DOI: 10.1016/j.stem.2024.10.011
Sophie Eichhorner, Larissa Traxler, Oliver Borgogno, Jerome Mertens
Studies from Ionescu et al.1 and Clayton et al.2 using multiple sclerosis (MS) patient-derived cell models underscore cholesterol metabolism’s role in inflammatory and dysfunctional cell phenotypes in the disease. Inhibiting cholesterol biosynthesis ameliorated critical cellular phenotypes, emphasizing the need to further investigate this pathway as a potential target for MS treatment.
{"title":"All roads lead to cholesterol: Modulating lipid biosynthesis in multiple sclerosis patient-derived models","authors":"Sophie Eichhorner, Larissa Traxler, Oliver Borgogno, Jerome Mertens","doi":"10.1016/j.stem.2024.10.011","DOIUrl":"https://doi.org/10.1016/j.stem.2024.10.011","url":null,"abstract":"Studies from Ionescu et al.<span><span><sup>1</sup></span></span> and Clayton et al.<span><span><sup>2</sup></span></span> using multiple sclerosis (MS) patient-derived cell models underscore cholesterol metabolism’s role in inflammatory and dysfunctional cell phenotypes in the disease. Inhibiting cholesterol biosynthesis ameliorated critical cellular phenotypes, emphasizing the need to further investigate this pathway as a potential target for MS treatment.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"33 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-07DOI: 10.1016/j.stem.2024.10.006
Christopher Z.W. Lee, Francesca M. Spagnoli
Two recent publications in Cell Stem Cell, Yang et al.1 and Migliorini et al.,2 utilized pluripotent stem cell-derived co-culture systems to explore the role of macrophages within the pancreatic islet during development and disease states.
{"title":"Nurturing protectors: Macrophages in the human pancreatic islet","authors":"Christopher Z.W. Lee, Francesca M. Spagnoli","doi":"10.1016/j.stem.2024.10.006","DOIUrl":"https://doi.org/10.1016/j.stem.2024.10.006","url":null,"abstract":"Two recent publications in <em>Cell Stem Cell</em>, Yang et al.<span><span><sup>1</sup></span></span> and Migliorini et al.,<span><span><sup>2</sup></span></span> utilized pluripotent stem cell-derived co-culture systems to explore the role of macrophages within the pancreatic islet during development and disease states.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"68 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-07DOI: 10.1016/j.stem.2024.10.007
Chun Liu, Mengcheng Shen, Yanxia Liu, Amit Manhas, Shane Rui Zhao, Mao Zhang, Nadjet Belbachir, Lu Ren, Joe Z. Zhang, Arianne Caudal, Masataka Nishiga, Dilip Thomas, Angela Zhang, Huaxiao Yang, Yang Zhou, Mohamed Ameen, Nazish Sayed, June-Wha Rhee, Lei S. Qi, Joseph C. Wu
Doxorubicin is limited in its therapeutic utility due to its life-threatening cardiovascular side effects. Here, we present an integrated drug discovery pipeline combining human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs), CRISPR interference and activation (CRISPRi/a) bidirectional pooled screens, and a small-molecule screening to identify therapeutic targets mitigating doxorubicin-induced cardiotoxicity (DIC) without compromising its oncological effects. The screens revealed several previously unreported candidate genes contributing to DIC, including carbonic anhydrase 12 (CA12). Genetic inhibition of CA12 protected iCMs against DIC by improving cell survival, sarcomere structural integrity, contractile function, and calcium handling. Indisulam, a CA12 antagonist, can effectively attenuate DIC in iCMs, engineered heart tissue, and animal models. Mechanistically, doxorubicin-induced CA12 potentiated a glycolytic activation in cardiomyocytes, contributing to DIC by interfering with cellular metabolism and functions. Collectively, our study provides a roadmap for future drug discovery efforts, potentially leading to more targeted therapies with minimal off-target toxicity.
{"title":"CRISPRi/a screens in human iPSC-cardiomyocytes identify glycolytic activation as a druggable target for doxorubicin-induced cardiotoxicity","authors":"Chun Liu, Mengcheng Shen, Yanxia Liu, Amit Manhas, Shane Rui Zhao, Mao Zhang, Nadjet Belbachir, Lu Ren, Joe Z. Zhang, Arianne Caudal, Masataka Nishiga, Dilip Thomas, Angela Zhang, Huaxiao Yang, Yang Zhou, Mohamed Ameen, Nazish Sayed, June-Wha Rhee, Lei S. Qi, Joseph C. Wu","doi":"10.1016/j.stem.2024.10.007","DOIUrl":"https://doi.org/10.1016/j.stem.2024.10.007","url":null,"abstract":"Doxorubicin is limited in its therapeutic utility due to its life-threatening cardiovascular side effects. Here, we present an integrated drug discovery pipeline combining human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs), CRISPR interference and activation (CRISPRi/a) bidirectional pooled screens, and a small-molecule screening to identify therapeutic targets mitigating doxorubicin-induced cardiotoxicity (DIC) without compromising its oncological effects. The screens revealed several previously unreported candidate genes contributing to DIC, including carbonic anhydrase 12 (CA12). Genetic inhibition of CA12 protected iCMs against DIC by improving cell survival, sarcomere structural integrity, contractile function, and calcium handling. Indisulam, a CA12 antagonist, can effectively attenuate DIC in iCMs, engineered heart tissue, and animal models. Mechanistically, doxorubicin-induced CA12 potentiated a glycolytic activation in cardiomyocytes, contributing to DIC by interfering with cellular metabolism and functions. Collectively, our study provides a roadmap for future drug discovery efforts, potentially leading to more targeted therapies with minimal off-target toxicity.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"149 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-07DOI: 10.1016/j.stem.2024.10.009
S.M. Yin, D.L. Li
Epitope editing is a promising strategy for protecting hematopoietic cells from eradication by immunotherapies. Recently, in Cell Stem Cell, Ji et al. applied both base editing (BE) and prime editing (PE) to alter the epitope of CD123 in hematopoietic stem cells for CAR-T therapy against acute myeloid leukemia.1
{"title":"To BE or to PE: Prime editors provide more choices for epitope-editing-based immunotherapy","authors":"S.M. Yin, D.L. Li","doi":"10.1016/j.stem.2024.10.009","DOIUrl":"https://doi.org/10.1016/j.stem.2024.10.009","url":null,"abstract":"Epitope editing is a promising strategy for protecting hematopoietic cells from eradication by immunotherapies. Recently, in <em>Cell Stem Cell</em>, Ji et al. applied both base editing (BE) and prime editing (PE) to alter the epitope of CD123 in hematopoietic stem cells for CAR-T therapy against acute myeloid leukemia.<span><span><sup>1</sup></span></span>","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"33 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-07DOI: 10.1016/j.stem.2024.10.008
Mihai G. Netea, Leo A.B. Joosten
An inappropriate induction of trained immunity in the bone marrow progenitors of immune cells has been described to underlie chronic inflammatory processes. Mills and colleagues’ recently published paper in Cell Stem Cell shows that maladaptive trained immunity drives inflammation in autoimmune processes,1 opening a new area of research in autoimmunity.
{"title":"Trained immunity in the bone marrow: Hub of autoimmunity","authors":"Mihai G. Netea, Leo A.B. Joosten","doi":"10.1016/j.stem.2024.10.008","DOIUrl":"https://doi.org/10.1016/j.stem.2024.10.008","url":null,"abstract":"An inappropriate induction of trained immunity in the bone marrow progenitors of immune cells has been described to underlie chronic inflammatory processes. Mills and colleagues’ recently published paper in <em>Cell Stem Cell</em> shows that maladaptive trained immunity drives inflammation in autoimmune processes,<span><span><sup>1</sup></span></span> opening a new area of research in autoimmunity.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"9 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-07DOI: 10.1016/j.stem.2024.09.019
Hafez Ismaili M’hamdi, Guido de Wert
The Dutch Health Council has advised to extend the 14-day rule to 28 days and to subsume integrated stem cell-based embryo models under the same legislative regime as natural embryos. Public discussion is necessary due to the ethical issues that may emerge from studying integrated and non-integrated embryo models.
{"title":"Reconsidering the 14-day rule in human embryo research: Advice from the Dutch Health Council","authors":"Hafez Ismaili M’hamdi, Guido de Wert","doi":"10.1016/j.stem.2024.09.019","DOIUrl":"https://doi.org/10.1016/j.stem.2024.09.019","url":null,"abstract":"The Dutch Health Council has advised to extend the 14-day rule to 28 days and to subsume integrated stem cell-based embryo models under the same legislative regime as natural embryos. Public discussion is necessary due to the ethical issues that may emerge from studying integrated and non-integrated embryo models.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"47 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-05DOI: 10.1016/j.stem.2024.10.004
Ran Jing, Marcelo Falchetti, Tianxiao Han, Mohamad Najia, Luca T. Hensch, Eleanor Meader, Edroaldo Lummertz da Rocha, Martin Kononov, Stephanie Wang, Trevor Bingham, Zhiheng Li, Yunliang Zhao, Katie Frenis, Caroline Kubaczka, Song Yang, Deepak Jha, Gabriela F. Rodrigues-Luiz, R. Grant Rowe, Thorsten M. Schlaeger, Marcela V. Maus, George Q. Daley
Elucidating mechanisms of T cell development can guide in vitro T cell differentiation from induced pluripotent stem cells (iPSCs) and facilitate off-the-shelf T cell-based immunotherapies. Using a stroma-free human iPSC-T cell differentiation platform, we screened for epigenetic modulators that influence T cell specification and identified the H3K9-directed histone methyltransferases G9a/GLP as repressors of T cell fate. We show that G9a/GLP inhibition during specific time windows of differentiation of hematopoietic stem and progenitor cells (HSPCs) skews cell fates toward lymphoid lineages. Inhibition of G9a/GLP promotes the production of lymphoid cells during zebrafish embryonic hematopoiesis, demonstrating the evolutionary conservation of G9a/GLP function. Importantly, chemical inhibition of G9a/GLP facilitates the generation of mature iPSC-T cells that bear transcriptional similarity to peripheral blood αβ T cells. When engineered to express chimeric antigen receptors, the epigenetically engineered iPSC-T cells exhibit enhanced effector functions in vitro and durable, persistent antitumor activity in a xenograft tumor-rechallenge model.
阐明T细胞的发育机制可以指导诱导多能干细胞（iPSC）的体外T细胞分化，并促进基于T细胞的现成免疫疗法。利用无基质的人类 iPSC-T 细胞分化平台，我们筛选了影响 T 细胞分化的表观遗传调节剂，并确定了 H3K9 引导的组蛋白甲基转移酶 G9a/GLP 是 T 细胞命运的抑制因子。我们发现，在造血干细胞和祖细胞（HSPCs）分化的特定时间窗口抑制 G9a/GLP 会使细胞命运向淋巴系倾斜。在斑马鱼胚胎造血过程中，抑制 G9a/GLP 可促进淋巴细胞的产生，这证明了 G9a/GLP 功能的进化保护。重要的是，化学抑制 G9a/GLP 可促进成熟 iPSC-T 细胞的生成，这些细胞与外周血 αβ T 细胞具有转录相似性。当被设计表达嵌合抗原受体时，经表观遗传学设计的 iPSC-T 细胞在体外表现出更强的效应功能，并在异种移植肿瘤挑战模型中表现出持久的抗肿瘤活性。
{"title":"Maturation and persistence of CAR T cells derived from human pluripotent stem cells via chemical inhibition of G9a/GLP","authors":"Ran Jing, Marcelo Falchetti, Tianxiao Han, Mohamad Najia, Luca T. Hensch, Eleanor Meader, Edroaldo Lummertz da Rocha, Martin Kononov, Stephanie Wang, Trevor Bingham, Zhiheng Li, Yunliang Zhao, Katie Frenis, Caroline Kubaczka, Song Yang, Deepak Jha, Gabriela F. Rodrigues-Luiz, R. Grant Rowe, Thorsten M. Schlaeger, Marcela V. Maus, George Q. Daley","doi":"10.1016/j.stem.2024.10.004","DOIUrl":"https://doi.org/10.1016/j.stem.2024.10.004","url":null,"abstract":"Elucidating mechanisms of T cell development can guide <em>in vitro</em> T cell differentiation from induced pluripotent stem cells (iPSCs) and facilitate off-the-shelf T cell-based immunotherapies. Using a stroma-free human iPSC-T cell differentiation platform, we screened for epigenetic modulators that influence T cell specification and identified the H3K9-directed histone methyltransferases G9a/GLP as repressors of T cell fate. We show that G9a/GLP inhibition during specific time windows of differentiation of hematopoietic stem and progenitor cells (HSPCs) skews cell fates toward lymphoid lineages. Inhibition of G9a/GLP promotes the production of lymphoid cells during zebrafish embryonic hematopoiesis, demonstrating the evolutionary conservation of G9a/GLP function. Importantly, chemical inhibition of G9a/GLP facilitates the generation of mature iPSC-T cells that bear transcriptional similarity to peripheral blood αβ T cells. When engineered to express chimeric antigen receptors, the epigenetically engineered iPSC-T cells exhibit enhanced effector functions <em>in vitro</em> and durable, persistent antitumor activity in a xenograft tumor-rechallenge model.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"84 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-04DOI: 10.1016/j.stem.2024.10.005
Antara Rao, Nuo Chen, Min Joo Kim, Jessica Blumenfeld, Oscar Yip, Zherui Liang, David Shostak, Yanxia Hao, Maxine R. Nelson, Nicole Koutsodendris, Brian Grone, Leo Ding, Seo Yeon Yoon, Patrick Arriola, Misha Zilberter, Yadong Huang
Despite strong evidence supporting the important roles of both apolipoprotein E4 (APOE4) and microglia in Alzheimer’s disease (AD) pathogenesis, the effects of microglia on neuronal APOE4-related AD pathogenesis remain elusive. To examine such effects, we utilized microglial depletion in a chimeric model with induced pluripotent stem cell (iPSC)-derived human neurons in mouse hippocampus. Specifically, we transplanted homozygous APOE4, isogenic APOE3, and APOE-knockout (APOE-KO) iPSC-derived human neurons into the hippocampus of human APOE3 or APOE4 knockin mice and then depleted microglia in half of the chimeric mice. We found that both neuronal APOE and microglial presence were important for the formation of Aβ and tau pathologies in an APOE isoform-dependent manner (APOE4 > APOE3). Single-cell RNA sequencing analysis identified two pro-inflammatory microglial subtypes with elevated MHC-II gene expression enriched in chimeric mice with human APOE4 neuron transplants. These findings highlight the concerted roles of neuronal APOE, especially APOE4, and microglia in AD pathogenesis.
{"title":"Microglia depletion reduces human neuronal APOE4-related pathologies in a chimeric Alzheimer’s disease model","authors":"Antara Rao, Nuo Chen, Min Joo Kim, Jessica Blumenfeld, Oscar Yip, Zherui Liang, David Shostak, Yanxia Hao, Maxine R. Nelson, Nicole Koutsodendris, Brian Grone, Leo Ding, Seo Yeon Yoon, Patrick Arriola, Misha Zilberter, Yadong Huang","doi":"10.1016/j.stem.2024.10.005","DOIUrl":"https://doi.org/10.1016/j.stem.2024.10.005","url":null,"abstract":"Despite strong evidence supporting the important roles of both apolipoprotein E4 (APOE4) and microglia in Alzheimer’s disease (AD) pathogenesis, the effects of microglia on neuronal APOE4-related AD pathogenesis remain elusive. To examine such effects, we utilized microglial depletion in a chimeric model with induced pluripotent stem cell (iPSC)-derived human neurons in mouse hippocampus. Specifically, we transplanted homozygous APOE4, isogenic APOE3, and APOE-knockout (APOE-KO) iPSC-derived human neurons into the hippocampus of human APOE3 or APOE4 knockin mice and then depleted microglia in half of the chimeric mice. We found that both neuronal APOE and microglial presence were important for the formation of Aβ and tau pathologies in an APOE isoform-dependent manner (APOE4 > APOE3). Single-cell RNA sequencing analysis identified two pro-inflammatory microglial subtypes with elevated MHC-II gene expression enriched in chimeric mice with human APOE4 neuron transplants. These findings highlight the concerted roles of neuronal APOE, especially APOE4, and microglia in AD pathogenesis.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"68 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-29DOI: 10.1016/j.stem.2024.10.002
Feng Zhang, Yao Fu, Dennisse Jimenez-Cyrus, Ting Zhao, Yachen Shen, Yusha Sun, Zhijian Zhang, Qing Wang, Riki Kawaguchi, Daniel H. Geschwind, Chuan He, Guo-li Ming, Hongjun Song
Quiescence acquisition of proliferating neural stem cells (NSCs) is required to establish the adult NSC pool. The underlying molecular mechanisms are not well understood. Here, we showed that conditional deletion of the m6A reader Ythdf2, which promotes mRNA decay, in proliferating NSCs in the early postnatal mouse hippocampus elevated quiescence acquisition in a cell-autonomous fashion with decreased neurogenesis. Multimodal profiling of m6A modification, YTHDF2 binding, and mRNA decay in hippocampal NSCs identified shared targets in multiple transforming growth factor β (TGF-β)-signaling-pathway components, including TGF-β ligands, maturation factors, receptors, transcription regulators, and signaling regulators. Functionally, Ythdf2 deletion led to TGF-β-signaling activation in NSCs, suppression of which rescued elevated quiescence acquisition of proliferating hippocampal NSCs. Our study reveals the dynamic nature and critical roles of mRNA decay in establishing the quiescent adult hippocampal NSC pool and uncovers a distinct mode of epitranscriptomic control via co-regulation of multiple components of the same signaling pathway.
{"title":"m6A/YTHDF2-mediated mRNA decay targets TGF-β signaling to suppress the quiescence acquisition of early postnatal mouse hippocampal NSCs","authors":"Feng Zhang, Yao Fu, Dennisse Jimenez-Cyrus, Ting Zhao, Yachen Shen, Yusha Sun, Zhijian Zhang, Qing Wang, Riki Kawaguchi, Daniel H. Geschwind, Chuan He, Guo-li Ming, Hongjun Song","doi":"10.1016/j.stem.2024.10.002","DOIUrl":"https://doi.org/10.1016/j.stem.2024.10.002","url":null,"abstract":"Quiescence acquisition of proliferating neural stem cells (NSCs) is required to establish the adult NSC pool. The underlying molecular mechanisms are not well understood. Here, we showed that conditional deletion of the m<sup>6</sup>A reader <em>Ythdf2</em>, which promotes mRNA decay, in proliferating NSCs in the early postnatal mouse hippocampus elevated quiescence acquisition in a cell-autonomous fashion with decreased neurogenesis. Multimodal profiling of m<sup>6</sup>A modification, YTHDF2 binding, and mRNA decay in hippocampal NSCs identified shared targets in multiple transforming growth factor β (TGF-β)-signaling-pathway components, including TGF-β ligands, maturation factors, receptors, transcription regulators, and signaling regulators. Functionally, <em>Ythdf2</em> deletion led to TGF-β-signaling activation in NSCs, suppression of which rescued elevated quiescence acquisition of proliferating hippocampal NSCs. Our study reveals the dynamic nature and critical roles of mRNA decay in establishing the quiescent adult hippocampal NSC pool and uncovers a distinct mode of epitranscriptomic control via co-regulation of multiple components of the same signaling pathway.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"14 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-24DOI: 10.1016/j.stem.2024.09.017
Massimo M. Onesto, Ji-il Kim, Sergiu P. Pasca
Neurodevelopment involves the migration, projection, and integration of various cell types across different regions of the nervous system. Assembloids are self-organizing systems formed by the integration of multiple organoids or cell types. Here, we outline the generation and application of assembloids. We illustrate how assembloids recapitulate critical neurodevelopmental steps, like migration, axon projection, and circuit formation, and how they are starting to provide biological insights into neuropsychiatric disorders. Additionally, we review how assembloids can be used to study properties emerging from cell-cell interactions within non-neural tissues. Overall, assembloid platforms represent a powerful tool for discovering human biology and developing therapeutics.
{"title":"Assembloid models of cell-cell interaction to study tissue and disease biology","authors":"Massimo M. Onesto, Ji-il Kim, Sergiu P. Pasca","doi":"10.1016/j.stem.2024.09.017","DOIUrl":"https://doi.org/10.1016/j.stem.2024.09.017","url":null,"abstract":"Neurodevelopment involves the migration, projection, and integration of various cell types across different regions of the nervous system. Assembloids are self-organizing systems formed by the integration of multiple organoids or cell types. Here, we outline the generation and application of assembloids. We illustrate how assembloids recapitulate critical neurodevelopmental steps, like migration, axon projection, and circuit formation, and how they are starting to provide biological insights into neuropsychiatric disorders. Additionally, we review how assembloids can be used to study properties emerging from cell-cell interactions within non-neural tissues. Overall, assembloid platforms represent a powerful tool for discovering human biology and developing therapeutics.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"30 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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