Cell stem cellPub Date : 2025-06-05DOI: 10.1016/j.stem.2025.05.006
Irene V. Choi, Rachel K. Zwick
{"title":"To play Paneth or goblet: Shapeshifting secretory cells read the room","authors":"Irene V. Choi, Rachel K. Zwick","doi":"10.1016/j.stem.2025.05.006","DOIUrl":"https://doi.org/10.1016/j.stem.2025.05.006","url":null,"abstract":"The intestinal secretory lineage is thought to comprise four distinct cell types derived from one Atoh1<sup>+</sup> progenitor, but the mechanisms that distinguish Paneth and goblet cells are unclear. Bhattacharya et al.<span><span><sup>1</sup></span></span> argue that these cells are instead phenotypic manifestations of a common terminal Atoh1<sup>+</sup> cell, actively shaped by niche-derived signals.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"12 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144219218","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}
Cell stem cellPub Date : 2025-06-05DOI: 10.1016/j.stem.2025.05.009
Danilo Tagle
{"title":"Prioritizing human tissue research: Q&A with Danilo Tagle","authors":"Danilo Tagle","doi":"10.1016/j.stem.2025.05.009","DOIUrl":"https://doi.org/10.1016/j.stem.2025.05.009","url":null,"abstract":"Recently, the US National Institutes of Health (NIH) announced an initiative to expand human-based research technologies and minimize animal use in research. Danilo Tagle, Director of the Office for Special Initiatives at the National Center for Advancing Translational Sciences, shares his perspective on the upcoming changes with <em>Cell Stem Cell</em>.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"9 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144219262","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}
Cell stem cellPub Date : 2025-06-05DOI: 10.1016/j.stem.2025.05.004
James Ellis, Knut Woltjen, Seema Mital, Megumu K. Saito, Akitsu Hotta, Jeanne F. Loring
{"title":"Diversifying the reference iPSC line concept","authors":"James Ellis, Knut Woltjen, Seema Mital, Megumu K. Saito, Akitsu Hotta, Jeanne F. Loring","doi":"10.1016/j.stem.2025.05.004","DOIUrl":"https://doi.org/10.1016/j.stem.2025.05.004","url":null,"abstract":"We discuss how to diversify the reference iPSC line concept. We highlight workflows for generating diverse iPSC lines. We ask whether reference lines can act as inclusive sources of human diversity for use in benchmarking controls for disease models or drug screens, or as clinical grade lines for cell therapies.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"31 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144219293","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}
Cell stem cellPub Date : 2025-06-04DOI: 10.1016/j.stem.2025.05.007
Martin P. Hosking, Soheila Shirinbak, Kyla Omilusik, Shilpi Chandra, Mika K. Kaneko, Angela Gentile, Susumu Yamamoto, Bishwas Shrestha, Joy Grant, Megan Boyett, Demetrio Cardenas, Hannah Keegan, Samad Ibitokou, Carolina Pavon, Takahiro Mizoguchi, Tatsuya Ihara, Daisuke Nakayama, Ramzey Abujarour, Tom T. Lee, Raedun Clarke, Bahram Valamehr
{"title":"Preferential tumor targeting of HER2 by iPSC-derived CAR T cells engineered to overcome multiple barriers to solid tumor efficacy","authors":"Martin P. Hosking, Soheila Shirinbak, Kyla Omilusik, Shilpi Chandra, Mika K. Kaneko, Angela Gentile, Susumu Yamamoto, Bishwas Shrestha, Joy Grant, Megan Boyett, Demetrio Cardenas, Hannah Keegan, Samad Ibitokou, Carolina Pavon, Takahiro Mizoguchi, Tatsuya Ihara, Daisuke Nakayama, Ramzey Abujarour, Tom T. Lee, Raedun Clarke, Bahram Valamehr","doi":"10.1016/j.stem.2025.05.007","DOIUrl":"https://doi.org/10.1016/j.stem.2025.05.007","url":null,"abstract":"Chimeric antigen receptor (CAR) T cell therapies in solid tumors have been limited by on-target, off-tumor toxicity, antigen heterogeneity, and an inability to simultaneously overcome multiple diverse resistance mechanisms within the tumor microenvironment that attenuate anti-tumor activity. Here, we describe an induced pluripotent stem cell (iPSC)-derived CAR T cell that combines a human epidermal growth factor receptor 2 (HER2)-targeting CAR—differentially recognizing tumor from normal cells and enabling detection of both truncated and misfolded HER2—with multiplex editing designed to address and overcome obstacles to maximize efficacy in solid tumor indications. The iPSC-derived, HER2-directed CAR T cells maintained potent HER2-specific anti-tumor activity in both <em>in vitro</em> and <em>in vivo</em> settings, with limited cytolytic targeting of HER2+ normal targets. Combination with therapeutic antibodies enabled comprehensive multi-antigen targeting through both the CAR and a high-affinity, non-cleavable CD16a Fc receptor. Additionally, specific engineering of interleukin (IL)-7R-fusion, transforming growth factor β (TGF-β)-IL-18R, and CXCR2 enabled sustained persistence, resistance to TGF-β-mediated suppression, and specific migration to the tumor.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"36 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211519","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}
{"title":"IGF2BP1 restricts the induction of human primordial germ cell fate in an m6A-dependent manner","authors":"Jin Zhang, Yashi Gu, Lingling Tong, Boshi Feng, Shenghua Dong, Qizhe Shao, Yanxi Chen, Huanchang Tu, Ziqi Wang, Yueqi Wang, Xiang Li, Honglin Yu, Ziying Lin, Xueting Wang, Zhenfu Li, Zhipeng Ai, Yangquan Xiang, Zhiwei Jiang, Zixin Jin, Zhengyi Li, Di Chen","doi":"10.1016/j.stem.2025.05.001","DOIUrl":"https://doi.org/10.1016/j.stem.2025.05.001","url":null,"abstract":"Primordial germ cells (PGCs) are specified early during embryogenesis and establish the germ cell lineage for transmitting genetic and epigenetic information from parents to offspring. However, whether <em>N</em><sup>6</sup>-methyladenosine (m<sup>6</sup>A)-mediated epigenetic regulation is involved in the specification of PGCs remains elusive. In this study, we report that a knockout of m<sup>6</sup>A writers or overexpression of m<sup>6</sup>A erasers leads to an increased percentage of human PGC-like cells (hPGCLCs) induced from embryonic stem cells using a 3D aggregate system. We identify the m<sup>6</sup>A reader IGF2BP1 as the key factor for restricting hPGCLC fate induction by stabilizing OTX2 mRNAs in an m<sup>6</sup>A-dependent manner. In turn, OTX2 protein suppresses the function of TFAP2C via histone variant MacroH2A.1 during germ cell lineage specification. We also observe a similar role of Igf2bp1 in zebrafish in the induction of PGC fate. In summary, we identify an m<sup>6</sup>A-IGF2BP1-OTX2-MacroH2A.1-TFAP2C signaling axis that restricts the specification of human germ cell fate.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"14 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145860","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}
Cell stem cellPub Date : 2025-05-22DOI: 10.1016/j.stem.2025.04.012
Maria Sirenko, Soobeom Lee, Zhengxi Sun, Ronan Chaligne, Sanam Loghavi, Georgios Asimomitis, Charlotte K. Brierley, Elsa Bernard, Sheng F. Cai, Robert M. Myers, Bettina Nadorp, Junya Sango, Morgan Lallo, Max F. Levine, Dylan Domenico, Juan E. Arango Ossa, Juan S. Medina-Martinez, Kamal Menghrajani, Audrey Lasry, Alice S. Mims, Elli Papaemmanuil
{"title":"Deconvoluting clonal and cellular architecture in IDH-mutant acute myeloid leukemia","authors":"Maria Sirenko, Soobeom Lee, Zhengxi Sun, Ronan Chaligne, Sanam Loghavi, Georgios Asimomitis, Charlotte K. Brierley, Elsa Bernard, Sheng F. Cai, Robert M. Myers, Bettina Nadorp, Junya Sango, Morgan Lallo, Max F. Levine, Dylan Domenico, Juan E. Arango Ossa, Juan S. Medina-Martinez, Kamal Menghrajani, Audrey Lasry, Alice S. Mims, Elli Papaemmanuil","doi":"10.1016/j.stem.2025.04.012","DOIUrl":"https://doi.org/10.1016/j.stem.2025.04.012","url":null,"abstract":"Isocitrate dehydrogenase 1/2 (<em>IDH</em>) mutations are early initiating events in acute myeloid leukemia (AML). The complex clonal architecture and cellular heterogeneity in <em>IDH-</em>mutant AML underlies the heterogeneous clinical presentation and outcomes. Integrating single-cell genotyping and transcriptomics, we demonstrate a stem-like and inflammatory phenotype of <em>IDH</em>-mutant AML and identify clone-specific programs associated with <em>NPM1</em>, <em>NRAS</em>, and <em>SRSF2</em> co-mutations. Furthermore, these clones had distinct responses to treatment with combination IDH inhibitors and chemotherapy, including elimination, reconstitution of myeloid differentiation, or retention within progenitor populations. At relapse after IDH inhibitor monotherapy, we identify upregulated stemness, inflammation, mitochondrial metabolism, and anti-apoptotic factors, as well as downregulated major histocompatibility complex (MHC) class II antigen presentation. At the pre-leukemic stage, we observe upregulation of <em>IDH2</em>-associated pathways, including inflammation. We deliver a detailed phenotyping of <em>IDH</em>-mutant AML and a framework for dissecting contributions of recurrently mutated genes in AML at diagnosis and following therapy, with implications for precision medicine.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"15 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144114404","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}
Cell stem cellPub Date : 2025-05-21DOI: 10.1016/j.stem.2025.04.010
Wei-Chien Yuan, Andrew S. Earl, Sai Ma, Karel Alcedo, Jacquelyn O. Russell, Fabiana M. Duarte, Yen-Ting Chu, Pei-Chi Chang, Hsin-Yi Chen, Hsin-Hui Chi, Qian Zhu, Alejo E. Rodriguez-Fraticelli, Sachin H. Patel, Yu-Ru Lee, Jason D. Buenrostro, Fernando D. Camargo
{"title":"HBO1 functions as an epigenetic barrier to hepatocyte plasticity and reprogramming during liver injury","authors":"Wei-Chien Yuan, Andrew S. Earl, Sai Ma, Karel Alcedo, Jacquelyn O. Russell, Fabiana M. Duarte, Yen-Ting Chu, Pei-Chi Chang, Hsin-Yi Chen, Hsin-Hui Chi, Qian Zhu, Alejo E. Rodriguez-Fraticelli, Sachin H. Patel, Yu-Ru Lee, Jason D. Buenrostro, Fernando D. Camargo","doi":"10.1016/j.stem.2025.04.010","DOIUrl":"https://doi.org/10.1016/j.stem.2025.04.010","url":null,"abstract":"Hepatocytes can reprogram into biliary epithelial cells (BECs) during liver injury, but the underlying epigenetic mechanisms remain poorly understood. Here, we define the chromatin dynamics of this process using single-cell ATAC-seq and identify YAP/TEAD activation as a key driver of chromatin remodeling. An <em>in vivo</em> CRISPR screen highlights the histone acetyltransferase HBO1 as a critical barrier to reprogramming. HBO1 is recruited by YAP to target loci, where it promotes histone H3 lysine 14 acetylation (H3K14ac) and engages the chromatin reader zinc-finger MYND-type containing 8 (ZMYND8) to suppress YAP/TEAD-driven transcription. Loss of HBO1 accelerates chromatin remodeling, enhances YAP binding, and enables a more complete hepatocyte-to-BEC transition. Our findings position HBO1 as an epigenetic brake that restrains YAP-mediated reprogramming, suggesting that targeting HBO1 may enhance hepatocyte plasticity for liver regeneration.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"15 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103992","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}
Cell stem cellPub Date : 2025-05-14DOI: 10.1016/j.stem.2025.04.011
Tao Luo, Cong Liu, Tao Cheng, Guo-Qin Zhao, Ying Huang, Jing-Yun Luan, Junyu Guo, Xiang Liu, Yi-Fan Wang, Yang Dong, Yu Xiao, Enhui He, Rui-Zhen Sun, Xiuyu Chen, Jiekai Chen, Jun Ma, Sean Megason, Junfeng Ji, Peng-Fei Xu
{"title":"Establishing dorsal-ventral patterning in human neural tube organoids with synthetic organizers","authors":"Tao Luo, Cong Liu, Tao Cheng, Guo-Qin Zhao, Ying Huang, Jing-Yun Luan, Junyu Guo, Xiang Liu, Yi-Fan Wang, Yang Dong, Yu Xiao, Enhui He, Rui-Zhen Sun, Xiuyu Chen, Jiekai Chen, Jun Ma, Sean Megason, Junfeng Ji, Peng-Fei Xu","doi":"10.1016/j.stem.2025.04.011","DOIUrl":"https://doi.org/10.1016/j.stem.2025.04.011","url":null,"abstract":"Precise dorsal-ventral (D-V) patterning of the neural tube (NT) is essential for the development and function of the central nervous system. However, existing models for studying NT D-V patterning and related human diseases remain inadequate. Here, we present organizers derived from pluripotent stem cell aggregate fusion (“ORDER”), a method that establishes opposing BMP and SHH gradients within neural ectodermal cell aggregates. Using this approach, we generated NT organoids with ordered D-V patterning from both zebrafish and human pluripotent stem cells (hPSCs). Single-cell transcriptomic analysis revealed that the synthetic human NT organoids (hNTOs) closely resemble the human embryonic spinal cord at Carnegie stage 12 (CS12) and exhibit greater similarity to human NT than to mouse models. Furthermore, using the hNTO model, we demonstrated the critical role of WNT signaling in regulating intermediate progenitors, modeled TCTN2-related D-V patterning defects, and identified a rescue strategy.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"4 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143946269","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}
Cell stem cellPub Date : 2025-05-08DOI: 10.1016/j.stem.2025.04.008
Min Shi, Brittney Crouse, Nambirajan Sundaram, Naomi Pode Shakked, Konrad Thorner, Nathaniel M. King, Parna Dutta, Lioba Ester, Weitao Zhang, Vinothini Govindarajah, Raphael Kopan, Cristina Cebrian, Christopher N. Mayhew, Michael A. Helmrath, Joseph V. Bonventre, Kyle W. McCracken
{"title":"Integrating collecting systems in human kidney organoids through fusion of distal nephron to ureteric bud","authors":"Min Shi, Brittney Crouse, Nambirajan Sundaram, Naomi Pode Shakked, Konrad Thorner, Nathaniel M. King, Parna Dutta, Lioba Ester, Weitao Zhang, Vinothini Govindarajah, Raphael Kopan, Cristina Cebrian, Christopher N. Mayhew, Michael A. Helmrath, Joseph V. Bonventre, Kyle W. McCracken","doi":"10.1016/j.stem.2025.04.008","DOIUrl":"https://doi.org/10.1016/j.stem.2025.04.008","url":null,"abstract":"Kidneys maintain homeostasis through an array of parallel nephrons, which fuse during development to a system of collecting ducts (CDs), establishing the essential luminal pathway for excretion of metabolic waste. Human kidney organoids derived from pluripotent stem cells (human pluripotent stem cells [hPSCs]) generate nephrons that lack CDs and terminate as blind-ended tubules, limiting their functional potential. Here, we describe a developmentally inspired hPSC differentiation system that addresses this deficiency through assembly of induced nephrogenic mesenchyme with ureteric bud (UB) progenitors, leading to a CD network functionally integrated in kidney organoids through fusion with the distal tubule. The nephron fusion occurs stereotypically and is regulated by proximal-distal nephron patterning, which can be modulated through temporal manipulation of developmental pathways. This work provides a platform for interrogating the principles and mechanisms underlying nephron-UB fusion and a framework for engineering unobstructed nephrons with collecting systems, an important step toward <em>de novo</em> generation of functional kidney tissue.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"187 6 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920773","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}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
