Cell stem cell最新文献_第4页

Vascular network-inspired diffusible scaffolds for engineering functional midbrain organoids 血管网络激发的可扩散支架工程功能中脑类器官

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-03-17 DOI: 10.1016/j.stem.2025.02.010

Hongwei Cai, Chunhui Tian, Lei Chen, Yang Yang, Alfred Xuyang Sun, Kyle McCracken, Jason Tchieu, Mingxia Gu, Ken Mackie, Feng Guo

{"title":"Vascular network-inspired diffusible scaffolds for engineering functional midbrain organoids","authors":"Hongwei Cai, Chunhui Tian, Lei Chen, Yang Yang, Alfred Xuyang Sun, Kyle McCracken, Jason Tchieu, Mingxia Gu, Ken Mackie, Feng Guo","doi":"10.1016/j.stem.2025.02.010","DOIUrl":"https://doi.org/10.1016/j.stem.2025.02.010","url":null,"abstract":"Organoids, 3D organ-like tissue cultures derived from stem cells, show promising potential for developmental biology, drug discovery, and regenerative medicine. However, the function and phenotype of current organoids, especially neural organoids, are still limited by insufficient diffusion of oxygen, nutrients, metabolites, signaling molecules, and drugs. Herein, we present vascular network-inspired diffusible (VID) scaffolds to mimic physiological diffusion physics for generating functional organoids and phenotyping their drug response. Specifically, the VID scaffolds, 3D-printed meshed tubular channel networks, successfully engineer human midbrain organoids almost without necrosis and hypoxia in commonly used well plates. Compared with conventional organoids, these engineered organoids develop more physiologically relevant features and functions, including midbrain-specific identity, oxygen metabolism, neuronal maturation, and network activity. Moreover, these engineered organoids also better recapitulate pharmacological responses, such as neural activity changes to fentanyl exposure, compared with conventional organoids with significant diffusion limits. This platform may provide insights for organoid development and therapeutic innovation.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"25 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635602","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}

引用次数: 0

EZH1 repression generates mature iPSC-derived CAR T cells with enhanced antitumor activity EZH1抑制产生成熟的ipsc衍生的CAR - T细胞，具有增强的抗肿瘤活性

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-03-14 DOI: 10.1016/j.stem.2025.03.006

Ran Jing, Irene Scarfo, Mohamad Ali Najia, Edroaldo Lummertz da Rocha, Areum Han, Michael Sanborn, Trevor Bingham, Caroline Kubaczka, Deepak K. Jha, Marcelo Falchetti, Thorsten M. Schlaeger, Trista E. North, Marcela V. Maus, George Q. Daley

引用次数: 0

PSPC1 bridges cancer stemness and malignancy in acute myeloid leukemia PSPC1在急性髓性白血病中的癌干性和恶性之间起桥梁作用

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-03-06 DOI: 10.1016/j.stem.2025.02.006

Hsi-Wen Yeh, Yaw-Dong Lang, Hsin-Yi Lee, Yuh-Shan Jou

引用次数: 0

Stripe out for brain evolution: Astrocytes go human 大脑进化：星形胶质细胞走向人类

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-03-06 DOI: 10.1016/j.stem.2025.02.008

Lara López-González, Víctor Borrell

引用次数: 0

Fetal-like reversion in the regenerating intestine is regulated by mesenchymal asporin 在再生肠中，胎儿样的逆转是由间充质间质酶调节的

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-03-06 DOI: 10.1016/j.stem.2025.02.009

Sharif Iqbal, Simon Andersson, Ernesta Nesta, Nalle Pentinmikko, Ashish Kumar, Sawan Kumar Jha, Daniel Borshagovski, Anna Webb, Nadja Gebert, Emma W. Viitala, Alexandra Ritchie, Sandra Scharaw, Emilia Kuuluvainen, Hjalte L. Larsen, Tuure Saarinen, Anne Juuti, Ari Ristimäki, Michael Jeltsch, Alessandro Ori, Markku Varjosalo, Pekka Katajisto

{"title":"Fetal-like reversion in the regenerating intestine is regulated by mesenchymal asporin","authors":"Sharif Iqbal, Simon Andersson, Ernesta Nesta, Nalle Pentinmikko, Ashish Kumar, Sawan Kumar Jha, Daniel Borshagovski, Anna Webb, Nadja Gebert, Emma W. Viitala, Alexandra Ritchie, Sandra Scharaw, Emilia Kuuluvainen, Hjalte L. Larsen, Tuure Saarinen, Anne Juuti, Ari Ristimäki, Michael Jeltsch, Alessandro Ori, Markku Varjosalo, Pekka Katajisto","doi":"10.1016/j.stem.2025.02.009","DOIUrl":"https://doi.org/10.1016/j.stem.2025.02.009","url":null,"abstract":"Mesenchymal cells and the extracellular matrix (ECM) support epithelium during homeostasis and regeneration. However, the role of the mesenchyme in epithelial conversion into a fetal-like regenerative state after damage is not known. We modeled epithelial regeneration by culturing intestinal epithelium on decellularized small intestinal scaffolds (iECM) and identify asporin (Aspn), an ECM-bound proteoglycan, as a critical mediator of epithelial fetal-like reprogramming. After damage, transient increase in Aspn expression by the pericryptal fibroblasts induces epithelial transforming growth factor β (TGF-β)-signaling via CD44 and promotes timely epithelial reprogramming. Temporal control of Aspn is lost in old mice, and after damage, the persistently high level of Aspn stagnates epithelium in the regenerative state. Increase in Wnt signaling can resolve the stagnated regenerative program of the old epithelium, promoting restoration of tissue function. In summary, we establish a platform for modeling epithelial injury responses ex vivo and show that the mesenchymal Aspn-producing niche modulates tissue repair by regulating epithelial fetal-like reprogramming.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"33 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560861","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}

引用次数: 0

Autologous cells, no longer lost in translation 自体细胞，在翻译过程中不再丢失

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-03-06 DOI: 10.1016/j.stem.2025.02.004

Malin Parmar, Anna Falk

引用次数: 0

Overcoming gene dosage barriers in mammalian development: An imprinting balancing act 克服哺乳动物发育中的基因剂量障碍：印迹平衡行为

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-03-06 DOI: 10.1016/j.stem.2025.02.005

Zhengfeng Liu, Marisa S. Bartolomei

引用次数: 0

Coordinated differentiation of human intestinal organoids with functional enteric neurons and vasculature 具有功能性肠神经元和血管的人肠道类器官的协调分化

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-03-04 DOI: 10.1016/j.stem.2025.02.007

Charlie J. Childs, Holly M. Poling, Kevin Chen, Yu-Hwai Tsai, Angeline Wu, Abigail Vallie, Madeline K. Eiken, Sha Huang, Caden W. Sweet, Ryan Schreiner, Zhiwei Xiao, Ryan C. Spencer, Samantha A. Paris, Ansley S. Conchola, Jonathan W. Villanueva, Meghan F. Anderman, Emily M. Holloway, Akaljot Singh, Roman J. Giger, Maxime M. Mahe, Jason R. Spence

{"title":"Coordinated differentiation of human intestinal organoids with functional enteric neurons and vasculature","authors":"Charlie J. Childs, Holly M. Poling, Kevin Chen, Yu-Hwai Tsai, Angeline Wu, Abigail Vallie, Madeline K. Eiken, Sha Huang, Caden W. Sweet, Ryan Schreiner, Zhiwei Xiao, Ryan C. Spencer, Samantha A. Paris, Ansley S. Conchola, Jonathan W. Villanueva, Meghan F. Anderman, Emily M. Holloway, Akaljot Singh, Roman J. Giger, Maxime M. Mahe, Jason R. Spence","doi":"10.1016/j.stem.2025.02.007","DOIUrl":"https://doi.org/10.1016/j.stem.2025.02.007","url":null,"abstract":"Human intestinal organoids (HIOs) derived from human pluripotent stem cells co-differentiate both epithelial and mesenchymal lineages in vitro but lack important cell types such as neurons, endothelial cells, and smooth muscle, which limits translational potential. Here, we demonstrate that the intestinal stem cell niche factor, EPIREGULIN (EREG), enhances HIO differentiation with epithelium, mesenchyme, enteric neuroglial populations, endothelial cells, and organized smooth muscle in a single differentiation, without the need for co-culture. When transplanted into a murine host, HIOs mature and demonstrate enteric nervous system function, undergoing peristaltic-like contractions indicative of a functional neuromuscular unit. HIOs also form functional vasculature, demonstrated in vitro using microfluidic devices and in vivo following transplantation, where HIO endothelial cells anastomose with host vasculature. These complex HIOs represent a transformative tool for translational research in the human gut and can be used to interrogate complex diseases as well as for testing therapeutic interventions with high fidelity to human pathophysiology.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"85 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538715","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}

引用次数: 0

Inhibition of PRC2 enables self-renewal of blastoid-competent naive pluripotent stem cells from chimpanzee 抑制PRC2可使黑猩猩胚状能幼稚多能干细胞自我更新

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-02-26 DOI: 10.1016/j.stem.2025.02.002

Tao Huang, Arthur Radley, Ayaka Yanagida, Zhili Ren, Francesca Carlisle, Somayyeh Tahajjodi, Dongwan Kim, Paul O’Neill, James Clarke, Madeline A. Lancaster, Zoe Heckhausen, Jingran Zhuo, João Pedro Agostinho de Sousa, Petra Hajkova, Ferdinand von Meyenn, Hiroo Imai, Hiromitsu Nakauchi, Ge Guo, Austin Smith, Hideki Masaki

{"title":"Inhibition of PRC2 enables self-renewal of blastoid-competent naive pluripotent stem cells from chimpanzee","authors":"Tao Huang, Arthur Radley, Ayaka Yanagida, Zhili Ren, Francesca Carlisle, Somayyeh Tahajjodi, Dongwan Kim, Paul O’Neill, James Clarke, Madeline A. Lancaster, Zoe Heckhausen, Jingran Zhuo, João Pedro Agostinho de Sousa, Petra Hajkova, Ferdinand von Meyenn, Hiroo Imai, Hiromitsu Nakauchi, Ge Guo, Austin Smith, Hideki Masaki","doi":"10.1016/j.stem.2025.02.002","DOIUrl":"https://doi.org/10.1016/j.stem.2025.02.002","url":null,"abstract":"Naive pluripotent stem cells (PSCs) are counterparts of early epiblast in the mammalian embryo. Mouse and human naive PSCs differ in self-renewal requirements and extraembryonic lineage potency. Here, we investigated the generation of chimpanzee naive PSCs. Colonies generated by resetting or reprogramming failed to propagate. We discovered that self-renewal is enabled by inhibition of Polycomb repressive complex 2 (PRC2). Expanded cells show global transcriptome proximity to human naive PSCs and embryo pre-implantation epiblast, with shared expression of a subset of pluripotency transcription factors. Chimpanzee naive PSCs can transition to multilineage competence or can differentiate into trophectoderm and hypoblast, forming tri-lineage blastoids. They thus provide a higher primate comparative model for studying pluripotency and early embryogenesis. Genetic deletions confirm that PRC2 mediates growth arrest. Further, inhibition of PRC2 overcomes a roadblock to feeder-free propagation of human naive PSCs. Therefore, excess deposition of chromatin modification H3K27me3 is an unexpected barrier to naive PSC self-renewal.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"22 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495780","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}

引用次数: 0

Pre-existing stem cell heterogeneity dictates clonal responses to the acquisition of leukemic driver mutations 预先存在的干细胞异质性决定了对白血病驱动突变获得的克隆反应

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-02-25 DOI: 10.1016/j.stem.2025.01.012

Indranil Singh, Daniel Fernandez-Perez, Pedro Sanchez Sanchez, Alejo E. Rodriguez-Fraticelli

{"title":"Pre-existing stem cell heterogeneity dictates clonal responses to the acquisition of leukemic driver mutations","authors":"Indranil Singh, Daniel Fernandez-Perez, Pedro Sanchez Sanchez, Alejo E. Rodriguez-Fraticelli","doi":"10.1016/j.stem.2025.01.012","DOIUrl":"https://doi.org/10.1016/j.stem.2025.01.012","url":null,"abstract":"Cancer cells display wide phenotypic variation even across patients with the same mutations. Differences in the cell of origin provide a potential explanation, but traditional assays lack the resolution to distinguish clonally heterogeneous subsets of stem and progenitor cells. To address this challenge, we developed simultaneous tracking of recombinase activation and clonal kinetics (STRACK), a method to trace clonal dynamics and gene expression before and after the acquisition of cancer mutations. Using mouse models, we studied two leukemic mutations, Dnmt3a-R878H and Npm1c, and found that their effect was highly variable across different stem cell states. Specifically, a subset of differentiation-primed stem cells, which normally becomes outcompeted with time, expands with both mutations. Intriguingly, Npm1c mutations reversed the intrinsic bias of the clone of origin, with differentiation-primed stem cells giving rise to more primitive malignant states. Thus, we highlight the relevance of single-cell lineage tracing to unravel early events in cancer evolution and posit that different cellular histories carry distinct cancer phenotypic potential.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"15 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143486529","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}

引用次数: 0