Cell stem cellPub Date : 2024-12-05DOI: 10.1016/j.stem.2024.11.007
Georgia Panagiotakos, Nan Yang
{"title":"Engineering regional diversity: A morphogen screen for patterned brain organoids","authors":"Georgia Panagiotakos, Nan Yang","doi":"10.1016/j.stem.2024.11.007","DOIUrl":"https://doi.org/10.1016/j.stem.2024.11.007","url":null,"abstract":"Morphogens orchestrate cellular diversity during nervous system development, yet a systematic approach to harnessing these signals in stem cell differentiation remains elusive. Amin et al.<span><span><sup>1</sup></span></span> present a platform integrating parallel morphogen modulator screening with single-cell sequencing of neural organoids, reinforcing brain regionalization principles and enabling detailed cellular annotation.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"40 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776474","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 : 2024-12-05DOI: 10.1016/j.stem.2024.11.012
Ioanna Mosialou, Stavroula Kousteni
{"title":"From brain to blood and back again: Linking chronic stress, myelopoiesis, and depression","authors":"Ioanna Mosialou, Stavroula Kousteni","doi":"10.1016/j.stem.2024.11.012","DOIUrl":"https://doi.org/10.1016/j.stem.2024.11.012","url":null,"abstract":"In this issue of <em>Cell Stem Cell</em>, Mou et al. identified a brain-bone marrow axis reinforcing myelopoiesis and neuroinflammation during psychological stress, culminating in depression. The identification of this pathway provides insights into hematopoietic stem cell homeostasis and regulatory neuronal function with potentially significant implications for the treatment of stress-related disorders.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"137 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776467","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 : 2024-12-05DOI: 10.1016/j.stem.2024.11.004
David F. Butler, Andrew S. Yoo
{"title":"Brain reboot: Enhancing neurogenesis and resilience","authors":"David F. Butler, Andrew S. Yoo","doi":"10.1016/j.stem.2024.11.004","DOIUrl":"https://doi.org/10.1016/j.stem.2024.11.004","url":null,"abstract":"In this issue of <em>Cell Stem Cell</em>, Shen et al. investigate <em>in vivo</em> transient expression of Yamanaka factors (YFs) during embryogenesis and an adult mouse model of Alzheimer’s disease (AD)-associated amyloidosis. These studies demonstrate that transient induction of YFs may be capable of enhancing neurogenesis and offer resilience against neurodegeneration.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"19 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776473","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 : 2024-12-05DOI: 10.1016/j.stem.2024.11.002
Aswathy Ammothumkandy, Luis Corona, Kristine Ravina, Victoria Wolseley, Jeremy Nelson, Nadiya Atai, Aidin Abedi, Nora Jimenez, Michelle Armacost, Lina M. D'Orazio, Virginia Zuverza-Chavarria, Alisha Cayce, Carol McCleary, George Nune, Laura Kalayjian, Darrin J. Lee, Brian Lee, Robert H. Chow, Christianne Heck, Jonathan J. Russin, Michael A. Bonaguidi
{"title":"Human adult neurogenesis loss corresponds with cognitive decline during epilepsy progression","authors":"Aswathy Ammothumkandy, Luis Corona, Kristine Ravina, Victoria Wolseley, Jeremy Nelson, Nadiya Atai, Aidin Abedi, Nora Jimenez, Michelle Armacost, Lina M. D'Orazio, Virginia Zuverza-Chavarria, Alisha Cayce, Carol McCleary, George Nune, Laura Kalayjian, Darrin J. Lee, Brian Lee, Robert H. Chow, Christianne Heck, Jonathan J. Russin, Michael A. Bonaguidi","doi":"10.1016/j.stem.2024.11.002","DOIUrl":"https://doi.org/10.1016/j.stem.2024.11.002","url":null,"abstract":"Mesial temporal lobe epilepsy (MTLE) is a syndromic disorder presenting with seizures and cognitive comorbidities. Although seizure etiology is increasingly understood, the pathophysiological mechanisms contributing to cognitive decline and epilepsy progression remain less recognized. We have previously shown that adult hippocampal neurogenesis dramatically declines in MTLE patients with increased disease duration. Here, we investigate when multiple cognitive domains become affected during epilepsy progression and how human neurogenesis levels contribute to it. We find that intelligence, verbal learning, and memory decline at a critical period of 20 years disease duration. In contrast to rodents, the number of human immature neurons positively associates with auditory verbal, rather than visuospatial, learning and memory. Moreover, this association does not apply to mature granule neurons. Our study provides cellular evidence of how adult neurogenesis corresponds with human cognition and signifies an opportunity to advance regenerative medicine for patients with MTLE and other cognitive disorders.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"36 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776745","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 : 2024-12-05DOI: 10.1016/j.stem.2024.11.008
Anna Bigas, Gayathri M. Kartha
{"title":"Making blood from iPSCs: Reaching for the most sought-after prize","authors":"Anna Bigas, Gayathri M. Kartha","doi":"10.1016/j.stem.2024.11.008","DOIUrl":"https://doi.org/10.1016/j.stem.2024.11.008","url":null,"abstract":"After many years of little progress, there is now hope for improved <em>in vitro</em> production of hematopoietic stem cells (HSCs). Ng et al.<span><span><sup>1</sup></span></span> have developed defined conditions that allow the generation of HSCs from induced pluripotent stem cells (iPSCs) with unprecedented blood-repopulating capacity.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"20 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776475","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 : 2024-12-05DOI: 10.1016/j.stem.2024.11.009
Milica Radisic
{"title":"Preventing radiation and chemo toxicity: Insights from bone marrow-on-a-chip","authors":"Milica Radisic","doi":"10.1016/j.stem.2024.11.009","DOIUrl":"https://doi.org/10.1016/j.stem.2024.11.009","url":null,"abstract":"Species-specific differences motivate the development of human hematopoiesis models. Georgescu et al.<span><span><sup>1</sup></span></span> present a microfluidic model of the human bone marrow perivascular niche to capture innate immune cell mobilization. Automated cultivation and high-content analysis for robust insights enabled studies of radiation injury and chemotherapy dosing.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"14 3-4 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776746","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 : 2024-12-05DOI: 10.1016/j.stem.2024.11.011
Eelco J.P. de Koning, Françoise Carlotti
{"title":"Stem cell islet replacement in type 1 diabetes: From “shelf” to “self”","authors":"Eelco J.P. de Koning, Françoise Carlotti","doi":"10.1016/j.stem.2024.11.011","DOIUrl":"https://doi.org/10.1016/j.stem.2024.11.011","url":null,"abstract":"Recently in <em>Cell</em>, Wang and colleagues<span><span><sup>1</sup></span></span> report the functional cure of a patient with type 1 diabetes after transplantation of autologous, induced pluripotent stem cell (iPSC)-derived islets in the rectus abdominis muscle.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"83 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776508","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 : 2024-12-05DOI: 10.1016/j.stem.2024.11.003
Andrei Georgescu, Joseph Hai Oved, Jonathan H. Galarraga, Thomas Cantrell, Samira Mehta, Brian M. Dulmovits, Timothy S. Olson, Pouria Fattahi, Anni Wang, Pelin L. Candarlioglu, Asli Muvaffak, Michele M. Kim, Sezin Aday Aydin, Jeongyun Seo, Eric S. Diffenderfer, Anthony Lynch, G. Scott Worthen, Dan Dongeun Huh
{"title":"Self-organization of the hematopoietic vascular niche and emergent innate immunity on a chip","authors":"Andrei Georgescu, Joseph Hai Oved, Jonathan H. Galarraga, Thomas Cantrell, Samira Mehta, Brian M. Dulmovits, Timothy S. Olson, Pouria Fattahi, Anni Wang, Pelin L. Candarlioglu, Asli Muvaffak, Michele M. Kim, Sezin Aday Aydin, Jeongyun Seo, Eric S. Diffenderfer, Anthony Lynch, G. Scott Worthen, Dan Dongeun Huh","doi":"10.1016/j.stem.2024.11.003","DOIUrl":"https://doi.org/10.1016/j.stem.2024.11.003","url":null,"abstract":"Here, we present a bioengineering approach to emulate the human bone marrow <em>in vitro</em>. Our developmentally inspired method uses self-organization of human hematopoietic stem and progenitor cells and vascular endothelial cells cultured in a three-dimensional microphysiological system to create vascularized, perfusable tissue constructs that resemble the hematopoietic vascular niche of the human marrow. The microengineered niche is capable of multilineage hematopoiesis and can generate functionally mature human myeloid cells that can intravasate into perfused blood vessels, providing a means to model the mobilization of innate immune cells from the marrow. We demonstrate the application of this system by presenting a specialized model of ionizing radiation-induced bone marrow injury and a multiorgan model of acute innate immune responses to bacterial lung infection. Furthermore, we introduce an advanced platform that enables large-scale integration and automated experimentation of the engineered hematopoietic tissues for preclinical screening of myelotoxicity due to anti-cancer drugs.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"77 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776507","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":"Generation of iPSC-derived human venous endothelial cells for the modeling of vascular malformations and drug discovery","authors":"Zihang Pan, Qiyang Yao, Weijing Kong, Xiaojing Ma, Liangliang Tian, Yun Zhao, Shuntian Zhu, Sheng Chen, Mengze Sun, Jiao Liu, Simin Jiang, Jianxun Ma, Qijia Liu, Xiaohong Peng, Xiaoxia Li, Zixuan Hong, Yi Hong, Xue Wang, Jiarui Liu, Jingjing Zhang, Kai Wang","doi":"10.1016/j.stem.2024.10.015","DOIUrl":"https://doi.org/10.1016/j.stem.2024.10.015","url":null,"abstract":"Venous malformations (VMs) represent prevalent vascular anomalies typically attributed to non-inherited somatic mutations within venous endothelial cells (VECs). The lack of robust disease models for VMs impedes drug discovery. Here, we devise a robust protocol for the generation of human induced VECs (iVECs) through manipulation of cell-cycle dynamics via the retinoic signaling pathway. We introduce an L914F mutation into the TIE2 gene locus of induced pluripotent stem cells (iPSCs) and show that the mutated iVECs form dilated blood vessels after transplantation into mice, thereby recapitulating the phenotypic characteristics observed in VMs. Moreover, utilizing a deep neural network and a high-throughput digital RNA with perturbation of genes sequencing (DRUG-seq) approach, we perform drug screening and demonstrate that bosutinib effectively rescues the disease phenotype <em>in vitro</em> and <em>in vivo</em>. In summary, by leveraging genome editing and stem cell technology, we generate VM models that enable the development of additional therapeutics.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"19 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690671","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 : 2024-11-12DOI: 10.1016/j.stem.2024.10.013
Daisuke Araki, Vicky Chen, Neelam Redekar, Christi Salisbury-Ruf, Yan Luo, Poching Liu, Yuesheng Li, Richard H. Smith, Pradeep Dagur, Christian Combs, Andre Larochelle
{"title":"Post-transplant G-CSF impedes engraftment of gene-edited human hematopoietic stem cells by exacerbating p53-mediated DNA damage response","authors":"Daisuke Araki, Vicky Chen, Neelam Redekar, Christi Salisbury-Ruf, Yan Luo, Poching Liu, Yuesheng Li, Richard H. Smith, Pradeep Dagur, Christian Combs, Andre Larochelle","doi":"10.1016/j.stem.2024.10.013","DOIUrl":"https://doi.org/10.1016/j.stem.2024.10.013","url":null,"abstract":"Granulocyte-colony-stimulating factor (G-CSF) is commonly used to accelerate recovery from neutropenia following chemotherapy and autologous transplantation of hematopoietic stem and progenitor cells (HSPCs) for malignant disorders. However, its utility after <em>ex vivo</em> gene therapy in human HSPCs remains unexplored. We show that administering G-CSF from day 1 to 14 post-transplant impedes engraftment of CRISPR-Cas9 gene-edited human HSPCs in murine xenograft models. G-CSF affects gene-edited HSPCs through a cell-intrinsic mechanism, causing proliferative stress and amplifying the early p53-mediated DNA damage response triggered by Cas9-mediated DNA double-strand breaks. This underscores a threshold mechanism where p53 activation must reach a critical level to impair cellular function. Transiently inhibiting p53 or delaying the initiation of G-CSF treatment to day 5 post-transplant attenuates its negative impact on gene-edited HSPCs. The potential for increased HSPC toxicity associated with post-transplant G-CSF administration in CRISPR-Cas9 autologous HSPC gene therapy warrants consideration in clinical trials.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"107 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599608","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}