Cell stem cell最新文献_第7页

Tunable differentiation of human CD4⁺ and CD8⁺ T cells from pluripotent stem cells. 人CD4+和CD8+ T细胞从多能干细胞的可调节分化。

IF 20.4

Cell stem cell Pub Date : 2026-01-08 DOI: 10.1016/j.stem.2025.12.010

Ross D Jones, Kevin Salim, Laura N Stankiewicz, John M Edgar, Lorna Leon, Jana K Gillies, Ali Murtaza, Lauren J Durland, Divy Raval, Charles Lau, Thristan Paulo B Taberna, Han Hsuan Hsu, Carla Zimmerman, Yale S Michaels, Fabio M V Rossi, Megan K Levings, Peter W Zandstra

{"title":"Tunable differentiation of human CD4+ and CD8+ T cells from pluripotent stem cells.","authors":"Ross D Jones, Kevin Salim, Laura N Stankiewicz, John M Edgar, Lorna Leon, Jana K Gillies, Ali Murtaza, Lauren J Durland, Divy Raval, Charles Lau, Thristan Paulo B Taberna, Han Hsuan Hsu, Carla Zimmerman, Yale S Michaels, Fabio M V Rossi, Megan K Levings, Peter W Zandstra","doi":"10.1016/j.stem.2025.12.010","DOIUrl":"10.1016/j.stem.2025.12.010","url":null,"abstract":"Allogeneic T cell therapies are a highly desirable option to circumvent the cost and complexity of using autologous T cells to treat diseases. Allogeneic CD8+ T cells can be made from pluripotent stem cells (PSCs), but deriving CD4+ T cells from PSCs has remained a significant challenge. Using feeder- and serum-free conditions, we found that CD4+ vs. CD8+ T cell commitment from PSCs can be controlled by fine-tuning the dynamics of Notch and T cell receptor (TCR) signaling delivered to CD4+CD8+ double-positive T cells. Notch signaling negatively impacts CD4+ T cell commitment, and its timed removal allows generation of clonally diverse and expandable CD4+ T cells from PSCs. The resulting CD4+ T cells respond to cytokine-mediated polarization by differentiating into Th1, Th2, or Th17 cells, recapitulating canonical helper cell function. These findings represent a significant step toward using PSC-derived CD4+ T cells as a low-cost, off-the-shelf cell therapy.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":"33 1","pages":"73-90.e14"},"PeriodicalIF":20.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145947060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Generation of human pineal gland organoids with melatonin production for disease modeling. 人类松果体类器官的生成与褪黑素的产生用于疾病建模。

IF 20.4

Cell stem cell Pub Date : 2026-01-08 Epub Date: 2025-12-30 DOI: 10.1016/j.stem.2025.12.004

Ferdi Ridvan Kiral, Woo Sub Yang, Onur Iyilikci, Xiaona Lu, Jonghun Kim, Mu Seog Choe, Cynthia Lo, Mei Zhong, Kun-Yong Kim, Yong-Hui Jiang, In-Hyun Park

{"title":"Generation of human pineal gland organoids with melatonin production for disease modeling.","authors":"Ferdi Ridvan Kiral, Woo Sub Yang, Onur Iyilikci, Xiaona Lu, Jonghun Kim, Mu Seog Choe, Cynthia Lo, Mei Zhong, Kun-Yong Kim, Yong-Hui Jiang, In-Hyun Park","doi":"10.1016/j.stem.2025.12.004","DOIUrl":"10.1016/j.stem.2025.12.004","url":null,"abstract":"The pineal gland regulates circadian rhythms through melatonin production, yet human studies are limited by poor tissue access. To overcome this, we developed human pineal gland organoids (hPGOs) from pluripotent stem cells, modeling pineal development and function. Single-cell RNA sequencing revealed distinct mature and developing pinealocyte populations with transcriptomic profiles closely resembling the in vivo pineal gland. hPGOs produce melatonin, express adrenergic receptors, and respond to noradrenaline, mimicking physiological regulation. To model disease-related impairments, we generated hPGOs from Angelman syndrome (AS) patient-derived iPSCs, which exhibit disrupted pinealocyte differentiation and markedly reduced melatonin synthesis, reflecting AS-related developmental pathology. Additionally, transplanted hPGOs restored circulating melatonin in pinealectomized mice, demonstrating their potential for cell-therapy approaches. These findings establish hPGOs as a robust platform for probing pineal development, circadian regulation, and their disruption in neurodevelopmental and sleep-related disorders.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"91-107.e9"},"PeriodicalIF":20.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12925488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Niche-preserving transplantation promotes functional engraftment of intestinal organoids in rat short bowel syndrome. 保留生态位移植促进大鼠短肠综合征肠道类器官的功能植入。

IF 20.4

Cell stem cell Pub Date : 2026-01-08 Epub Date: 2025-12-29 DOI: 10.1016/j.stem.2025.12.007

Ryoma Endo, Shinya Sugimoto, Yutaro Kuwashima, Mami Matano, Hikaru Hanyu, Sirirat Takahashi, Hirochika Kato, Taku Tanaka, Andreas Michael Sihombing, Koji Shirosaki, Yoshiko Hatano, Yuki Sugiura, Takanori Kanai, Motoshi Wada, Toshiro Sato

{"title":"Niche-preserving transplantation promotes functional engraftment of intestinal organoids in rat short bowel syndrome.","authors":"Ryoma Endo, Shinya Sugimoto, Yutaro Kuwashima, Mami Matano, Hikaru Hanyu, Sirirat Takahashi, Hirochika Kato, Taku Tanaka, Andreas Michael Sihombing, Koji Shirosaki, Yoshiko Hatano, Yuki Sugiura, Takanori Kanai, Motoshi Wada, Toshiro Sato","doi":"10.1016/j.stem.2025.12.007","DOIUrl":"10.1016/j.stem.2025.12.007","url":null,"abstract":"Short bowel syndrome (SBS) is a life-threatening condition in which outcomes often critically depend on ileal function, the only intestinal segment specialized for bile acid uptake and efficient fat absorption. However, whether restoring ileal epithelium-specific nutrient absorption can ameliorate SBS has remained unknown. Here, we demonstrate a niche-preserving transplantation strategy enabling highly efficient engraftment of intestinal organoids into the rat small intestine. Clearing luminal mucus with N-acetylcysteine facilitates ethylenediaminetetraacetic acid (EDTA)-based epithelial detachment, enabling removal of Lgr5+ stem cells while preserving the stromal niche. This preconditioning increased the engrafted area and enabled the generation of an ilealized jejunum that improved body-weight trajectories and survival in rat SBS. Furthermore, the engrafted epithelia endowed the jejunum with bile acid absorption capacity. These findings provide in vivo evidence for stem cell niche theory, showing that the niche is essential to accommodate donor stem cells, and establish ilealized jejunum as a path toward autologous, region-targeted therapy for SBS.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"157-165.e6"},"PeriodicalIF":20.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145866914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Patient iPSC models reveal glia-intrinsic phenotypes in multiple sclerosis. 患者 iPSC 模型揭示了多发性硬化症的神经胶质内表型。

IF 20.4

Cell stem cell Pub Date : 2024-11-07 Epub Date: 2024-08-26 DOI: 10.1016/j.stem.2024.08.002

Benjamin L L Clayton, Lilianne Barbar, Maria Sapar, Kriti Kalpana, Chandrika Rao, Bianca Migliori, Tomasz Rusielewicz, Daniel Paull, Katie Brenner, Dorota Moroziewicz, Ilana Katz Sand, Patrizia Casaccia, Paul J Tesar, Valentina Fossati

{"title":"Patient iPSC models reveal glia-intrinsic phenotypes in multiple sclerosis.","authors":"Benjamin L L Clayton, Lilianne Barbar, Maria Sapar, Kriti Kalpana, Chandrika Rao, Bianca Migliori, Tomasz Rusielewicz, Daniel Paull, Katie Brenner, Dorota Moroziewicz, Ilana Katz Sand, Patrizia Casaccia, Paul J Tesar, Valentina Fossati","doi":"10.1016/j.stem.2024.08.002","DOIUrl":"10.1016/j.stem.2024.08.002","url":null,"abstract":"Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system (CNS), resulting in neurological disability that worsens over time. While progress has been made in defining the immune system's role in MS pathophysiology, the contribution of intrinsic CNS cell dysfunction remains unclear. Here, we generated a collection of induced pluripotent stem cell (iPSC) lines from people with MS spanning diverse clinical subtypes and differentiated them into glia-enriched cultures. Using single-cell transcriptomic profiling and orthogonal analyses, we observed several distinguishing characteristics of MS cultures pointing to glia-intrinsic disease mechanisms. We found that primary progressive MS-derived cultures contained fewer oligodendrocytes. Moreover, MS-derived oligodendrocyte lineage cells and astrocytes showed increased expression of immune and inflammatory genes, matching those of glia from MS postmortem brains. Thus, iPSC-derived MS models provide a unique platform for dissecting glial contributions to disease phenotypes independent of the peripheral immune system and identify potential glia-specific targets for therapeutic intervention.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"1701-1713.e8"},"PeriodicalIF":20.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hallmarks of regeneration. 再生的标志

IF 20.4

Cell stem cell Pub Date : 2024-09-05 Epub Date: 2024-08-19 DOI: 10.1016/j.stem.2024.07.007

Kenneth D Poss, Elly M Tanaka

引用次数: 0

Integrated single-cell analysis defines the epigenetic basis of castration-resistant prostate luminal cells. 单细胞综合分析确定了耐阉割前列腺管腔细胞的表观遗传学基础。

IF 20.4

Cell stem cell Pub Date : 2024-08-01 Epub Date: 2024-06-14 DOI: 10.1016/j.stem.2024.05.008

Jason S Kirk, Jie Wang, Mark Long, Spencer Rosario, Amanda Tracz, Yibing Ji, Rahul Kumar, Xiaozhuo Liu, Anmbreen Jamroze, Prashant K Singh, Igor Puzanov, Gurkamal Chatta, Qing Cheng, Jiaoti Huang, Jeffrey L Wrana, Jonathan Lovell, Han Yu, Song Liu, Michael M Shen, Tao Liu, Dean G Tang

{"title":"Integrated single-cell analysis defines the epigenetic basis of castration-resistant prostate luminal cells.","authors":"Jason S Kirk, Jie Wang, Mark Long, Spencer Rosario, Amanda Tracz, Yibing Ji, Rahul Kumar, Xiaozhuo Liu, Anmbreen Jamroze, Prashant K Singh, Igor Puzanov, Gurkamal Chatta, Qing Cheng, Jiaoti Huang, Jeffrey L Wrana, Jonathan Lovell, Han Yu, Song Liu, Michael M Shen, Tao Liu, Dean G Tang","doi":"10.1016/j.stem.2024.05.008","DOIUrl":"10.1016/j.stem.2024.05.008","url":null,"abstract":"Understanding prostate response to castration and androgen receptor signaling inhibitors (ARSI) is critical to improving long-term prostate cancer (PCa) patient survival. Here, we use a multi-omics approach on 229,794 single cells to create a mouse single-cell reference atlas for interpreting mouse prostate biology and castration response. Our reference atlas refines single-cell annotations and provides a chromatin context, which, when coupled with mouse lineage tracing, demonstrates that castration-resistant luminal cells are distinct from the pre-existent urethra-proximal stem/progenitor cells. Molecular pathway analysis and therapeutic studies further implicate AP1 (JUN/FOS), WNT/β-catenin, FOXQ1, NF-κB, and JAK/STAT pathways as major drivers of castration-resistant luminal populations with relevance to human PCa. Our datasets, which can be explored through an interactive portal (https://visportal.roswellpark.org/data/tang/), can aid in developing combination treatments with ARSI for advanced PCa patients.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"1203-1221.e7"},"PeriodicalIF":20.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141328143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oscillation steers differentiation. 震荡引导分化。

IF 20.4

Cell stem cell Pub Date : 2024-07-05 DOI: 10.1016/j.stem.2024.06.008

Kyle A LaBella, Efren A Reyes, Louis Vermeulen

引用次数: 0

Monkey see, monkey do: Tracking iPS-cardiomyocyte survival and maturation in autografts. 猴子看，猴子干：跟踪 iPS 心肌细胞在自体移植物中的存活和成熟。

IF 20.4

Cell stem cell Pub Date : 2024-07-05 DOI: 10.1016/j.stem.2024.06.006

Xiaoqian Ji, Qiyuan Wang, Nan Cao

引用次数: 0

Cultivating awareness of donation in cutting-edge allogenic cell therapies. 在最前沿的异基因细胞疗法中培养捐赠意识。