Development has the answer: Unraveling psychiatric disorders via thalamocortical organoids
Cell Stem Cell. 2024 Mar 7;31(3):283-284. doi: 10.1016/j.stem.2024.02.008.ABSTRACTDissecting the role of the thalamus in neuropsychiatric disorders requires new models to analyze complex genetic interactions. In this issue of Cell Stem Cell, Shin et al. use patient-derived thalamocortical organoids to investigate 22q11.2 microdeletion impact on thalamic development, revealing significant transcriptional dysregulation linked to psychiatric disorders.PMID:38458174 | DOI:10.1016/j.stem.2024.02.008 (Source: Cell Stem Cell)
Source: Cell Stem Cell - March 8, 2024 Category: Stem Cells Authors: Eduardo Leyva-D íaz Emily S Wilson Guillermina L ópez-Bendito Source Type: research

From suppressor to enhancer: IL-10's alternative role in CAR-T cell therapies against solid tumors
Cell Stem Cell. 2024 Mar 7;31(3):285-287. doi: 10.1016/j.stem.2024.02.003.ABSTRACTAiming to improve the effector function of CAR-T cells, Zhao et al.1 report that IL-10 metabolically reprograms CAR-T cells, and this promotes their effectiveness against solid tumors and challenges IL-10's perceived role as merely immunosuppressive. This simple but promising strategy fosters durable immune memory and eagerly awaits validation in clinical trials.PMID:38458175 | DOI:10.1016/j.stem.2024.02.003 (Source: Cell Stem Cell)
Source: Cell Stem Cell - March 8, 2024 Category: Stem Cells Authors: Yuwei Huang Haopeng Wang Source Type: research

KOLF2.1J iPSCs carry CNVs associated with neurodevelopmental disorders
Cell Stem Cell. 2024 Mar 7;31(3):288-289. doi: 10.1016/j.stem.2024.02.007.NO ABSTRACTPMID:38458176 | DOI:10.1016/j.stem.2024.02.007 (Source: Cell Stem Cell)
Source: Cell Stem Cell - March 8, 2024 Category: Stem Cells Authors: Carolina Gracia-Diaz Jonathan E Perdomo Munir E Khan Thomas Roule Brianna L Disanza Gregory G Cajka Sunyimeng Lei Alyssa L Gagne Jean Ann Maguire Ophir Shalem Elizabeth J Bhoj Rebecca C Ahrens-Nicklas Deborah L French Ethan M Goldberg Kai Wang Joseph T Gl Source Type: research

Large structural variants in KOLF2.1J are unlikely to compromise neurological disease modeling
Cell Stem Cell. 2024 Mar 7;31(3):290-291. doi: 10.1016/j.stem.2024.02.006.NO ABSTRACTPMID:38458177 | DOI:10.1016/j.stem.2024.02.006 (Source: Cell Stem Cell)
Source: Cell Stem Cell - March 8, 2024 Category: Stem Cells Authors: Mallory Ryan Justin A McDonough Michael E Ward Mark R Cookson William C Skarnes Florian T Merkle Source Type: research

A mitochondrial NADPH-cholesterol axis regulates extracellular vesicle biogenesis to support hematopoietic stem cell fate
Cell Stem Cell. 2024 Mar 7;31(3):359-377.e10. doi: 10.1016/j.stem.2024.02.004.ABSTRACTMitochondrial fatty acid oxidation (FAO) is essential for hematopoietic stem cell (HSC) self-renewal; however, the mechanism by which mitochondrial metabolism controls HSC fate remains unknown. Here, we show that within the hematopoietic lineage, HSCs have the largest mitochondrial NADPH pools, which are required for proper HSC cell fate and homeostasis. Bioinformatic analysis of the HSC transcriptome, biochemical assays, and genetic inactivation of FAO all indicate that FAO-generated NADPH fuels cholesterol synthesis in HSCs. Interferenc...
Source: Cell Stem Cell - March 8, 2024 Category: Stem Cells Authors: Massimo Bonora Claudia Morganti Nick van Gastel Kyoko Ito Enrica Calura Ilaria Zanolla Letizia Ferroni Yang Zhang Yookyung Jung Gabriele Sales Paolo Martini Takahisa Nakamura Francesco Massimo Lasorsa Toren Finkel Charles P Lin Barbara Zavan Paolo Pinton Source Type: research

Preclinical efficacy and safety of encapsulated proliferating human hepatocyte organoids in treating liver failure
Cell Stem Cell. 2024 Feb 27:S1934-5909(24)00048-1. doi: 10.1016/j.stem.2024.02.005. Online ahead of print.ABSTRACTAlginate-encapsulated hepatocyte transplantation is a promising strategy to treat liver failure. However, its clinical application was impeded by the lack of primary human hepatocytes and difficulty in controlling their quality. We previously reported proliferating human hepatocytes (ProliHHs). Here, quality-controlled ProliHHs were produced in mass and engineered as liver organoids to improve their maturity. Encapsulated ProliHHs liver organoids (eLO) were intraperitoneally transplanted to treat liver failure ...
Source: Cell Stem Cell - March 8, 2024 Category: Stem Cells Authors: Xiang Yuan Jingqi Wu Zhen Sun Jin Cen Yajing Shu Chenhua Wang Hong Li Dongni Lin Kun Zhang Baihua Wu Anil Dhawan Ludi Zhang Lijian Hui Source Type: research

Promises and challenges of organoids: From humanized to human derived
Cell Stem Cell. 2024 Mar 7;31(3):281-282. doi: 10.1016/j.stem.2024.02.002.ABSTRACTKastenschmidt et al.1 present a groundbreaking organoid culture model for follicular lymphoma, which is capable of maintaining stable compositions of B and T cells. This model is utilized in testing bispecific antibodies in effective killing of tumor B cells with the activation of T cells.PMID:38458173 | DOI:10.1016/j.stem.2024.02.002 (Source: Cell Stem Cell)
Source: Cell Stem Cell - March 8, 2024 Category: Stem Cells Authors: Wenyan Wang Yang-Xin Fu Source Type: research

Development has the answer: Unraveling psychiatric disorders via thalamocortical organoids
Cell Stem Cell. 2024 Mar 7;31(3):283-284. doi: 10.1016/j.stem.2024.02.008.ABSTRACTDissecting the role of the thalamus in neuropsychiatric disorders requires new models to analyze complex genetic interactions. In this issue of Cell Stem Cell, Shin et al. use patient-derived thalamocortical organoids to investigate 22q11.2 microdeletion impact on thalamic development, revealing significant transcriptional dysregulation linked to psychiatric disorders.PMID:38458174 | DOI:10.1016/j.stem.2024.02.008 (Source: Cell Stem Cell)
Source: Cell Stem Cell - March 8, 2024 Category: Stem Cells Authors: Eduardo Leyva-D íaz Emily S Wilson Guillermina L ópez-Bendito Source Type: research

From suppressor to enhancer: IL-10's alternative role in CAR-T cell therapies against solid tumors
Cell Stem Cell. 2024 Mar 7;31(3):285-287. doi: 10.1016/j.stem.2024.02.003.ABSTRACTAiming to improve the effector function of CAR-T cells, Zhao et al.1 report that IL-10 metabolically reprograms CAR-T cells, and this promotes their effectiveness against solid tumors and challenges IL-10's perceived role as merely immunosuppressive. This simple but promising strategy fosters durable immune memory and eagerly awaits validation in clinical trials.PMID:38458175 | DOI:10.1016/j.stem.2024.02.003 (Source: Cell Stem Cell)
Source: Cell Stem Cell - March 8, 2024 Category: Stem Cells Authors: Yuwei Huang Haopeng Wang Source Type: research

KOLF2.1J iPSCs carry CNVs associated with neurodevelopmental disorders
Cell Stem Cell. 2024 Mar 7;31(3):288-289. doi: 10.1016/j.stem.2024.02.007.NO ABSTRACTPMID:38458176 | DOI:10.1016/j.stem.2024.02.007 (Source: Cell Stem Cell)
Source: Cell Stem Cell - March 8, 2024 Category: Stem Cells Authors: Carolina Gracia-Diaz Jonathan E Perdomo Munir E Khan Thomas Roule Brianna L Disanza Gregory G Cajka Sunyimeng Lei Alyssa L Gagne Jean Ann Maguire Ophir Shalem Elizabeth J Bhoj Rebecca C Ahrens-Nicklas Deborah L French Ethan M Goldberg Kai Wang Joseph T Gl Source Type: research

Large structural variants in KOLF2.1J are unlikely to compromise neurological disease modeling
Cell Stem Cell. 2024 Mar 7;31(3):290-291. doi: 10.1016/j.stem.2024.02.006.NO ABSTRACTPMID:38458177 | DOI:10.1016/j.stem.2024.02.006 (Source: Cell Stem Cell)
Source: Cell Stem Cell - March 8, 2024 Category: Stem Cells Authors: Mallory Ryan Justin A McDonough Michael E Ward Mark R Cookson William C Skarnes Florian T Merkle Source Type: research

A mitochondrial NADPH-cholesterol axis regulates extracellular vesicle biogenesis to support hematopoietic stem cell fate
Cell Stem Cell. 2024 Mar 7;31(3):359-377.e10. doi: 10.1016/j.stem.2024.02.004.ABSTRACTMitochondrial fatty acid oxidation (FAO) is essential for hematopoietic stem cell (HSC) self-renewal; however, the mechanism by which mitochondrial metabolism controls HSC fate remains unknown. Here, we show that within the hematopoietic lineage, HSCs have the largest mitochondrial NADPH pools, which are required for proper HSC cell fate and homeostasis. Bioinformatic analysis of the HSC transcriptome, biochemical assays, and genetic inactivation of FAO all indicate that FAO-generated NADPH fuels cholesterol synthesis in HSCs. Interferenc...
Source: Cell Stem Cell - March 8, 2024 Category: Stem Cells Authors: Massimo Bonora Claudia Morganti Nick van Gastel Kyoko Ito Enrica Calura Ilaria Zanolla Letizia Ferroni Yang Zhang Yookyung Jung Gabriele Sales Paolo Martini Takahisa Nakamura Francesco Massimo Lasorsa Toren Finkel Charles P Lin Barbara Zavan Paolo Pinton Source Type: research

Preclinical efficacy and safety of encapsulated proliferating human hepatocyte organoids in treating liver failure
Cell Stem Cell. 2024 Feb 27:S1934-5909(24)00048-1. doi: 10.1016/j.stem.2024.02.005. Online ahead of print.ABSTRACTAlginate-encapsulated hepatocyte transplantation is a promising strategy to treat liver failure. However, its clinical application was impeded by the lack of primary human hepatocytes and difficulty in controlling their quality. We previously reported proliferating human hepatocytes (ProliHHs). Here, quality-controlled ProliHHs were produced in mass and engineered as liver organoids to improve their maturity. Encapsulated ProliHHs liver organoids (eLO) were intraperitoneally transplanted to treat liver failure ...
Source: Cell Stem Cell - March 8, 2024 Category: Stem Cells Authors: Xiang Yuan Jingqi Wu Zhen Sun Jin Cen Yajing Shu Chenhua Wang Hong Li Dongni Lin Kun Zhang Baihua Wu Anil Dhawan Ludi Zhang Lijian Hui Source Type: research

An iron rheostat controls hematopoietic stem cell fate
Cell Stem Cell. 2024 Mar 7;31(3):378-397.e12. doi: 10.1016/j.stem.2024.01.011. Epub 2024 Feb 22.ABSTRACTMechanisms governing the maintenance of blood-producing hematopoietic stem and multipotent progenitor cells (HSPCs) are incompletely understood, particularly those regulating fate, ensuring long-term maintenance, and preventing aging-associated stem cell dysfunction. We uncovered a role for transitory free cytoplasmic iron as a rheostat for adult stem cell fate control. We found that HSPCs harbor comparatively small amounts of free iron and show the activation of a conserved molecular response to limited iron-particularl...
Source: Cell Stem Cell - February 25, 2024 Category: Stem Cells Authors: Yun-Ruei Kao Jiahao Chen Rajni Kumari Anita Ng Aliona Zintiridou Madhuri Tatiparthy Yuhong Ma Maria M Aivalioti Deeposree Moulik Sriram Sundaravel Daqian Sun Julie A Reisz Juliane Grimm Nuria Martinez-Lopez Stephanie Stransky Simone Sidoli Ulrich Steidl R Source Type: research

Region-specific cellular and molecular basis of liver regeneration after acute pericentral injury
Cell Stem Cell. 2024 Mar 7;31(3):341-358.e7. doi: 10.1016/j.stem.2024.01.013. Epub 2024 Feb 22.ABSTRACTLiver injuries often occur in a zonated manner. However, detailed regenerative responses to such zonal injuries at cellular and molecular levels remain largely elusive. By using a fate-mapping strain, Cyp2e1-DreER, to elucidate liver regeneration after acute pericentral injury, we found that pericentral regeneration is primarily compensated by the expansion of remaining pericentral hepatocytes, and secondarily by expansion of periportal hepatocytes. Employing single-cell RNA sequencing, spatial transcriptomics, immunostai...
Source: Cell Stem Cell - February 25, 2024 Category: Stem Cells Authors: Shuyong Wang Xuan Wang Yiran Shan Zuolong Tan Yuxin Su Yannan Cao Shuang Wang Jiahong Dong Jin Gu Yunfang Wang Source Type: research