Generation of human alveolar epithelial type I cells from pluripotent stem cells
Cell Stem Cell. 2024 Apr 15:S1934-5909(24)00098-5. doi: 10.1016/j.stem.2024.03.017. Online ahead of print.ABSTRACTAlveolar epithelial type I cells (AT1s) line the gas exchange barrier of the distal lung and have been historically challenging to isolate or maintain in cell culture. Here, we engineer a human in vitro AT1 model system via directed differentiation of induced pluripotent stem cells (iPSCs). We use primary adult AT1 global transcriptomes to suggest benchmarks and pathways, such as Hippo-LATS-YAP/TAZ signaling, enriched in these cells. Next, we generate iPSC-derived alveolar epithelial type II cells (AT2s) and fi...
Source: Cell Stem Cell - April 20, 2024 Category: Stem Cells Authors: Claire L Burgess Jessie Huang Pushpinder S Bawa Konstantinos-Dionysios Alysandratos Kasey Minakin Lauren J Ayers Michael P Morley Apoorva Babu Carlos Villacorta-Martin Maria Yampolskaya Anne Hinds Bibek R Thapa Feiya Wang Adeline Matschulat Pankaj Mehta E Source Type: research

Generation of human alveolar epithelial type I cells from pluripotent stem cells
Cell Stem Cell. 2024 Apr 15:S1934-5909(24)00098-5. doi: 10.1016/j.stem.2024.03.017. Online ahead of print.ABSTRACTAlveolar epithelial type I cells (AT1s) line the gas exchange barrier of the distal lung and have been historically challenging to isolate or maintain in cell culture. Here, we engineer a human in vitro AT1 model system via directed differentiation of induced pluripotent stem cells (iPSCs). We use primary adult AT1 global transcriptomes to suggest benchmarks and pathways, such as Hippo-LATS-YAP/TAZ signaling, enriched in these cells. Next, we generate iPSC-derived alveolar epithelial type II cells (AT2s) and fi...
Source: Cell Stem Cell - April 20, 2024 Category: Stem Cells Authors: Claire L Burgess Jessie Huang Pushpinder S Bawa Konstantinos-Dionysios Alysandratos Kasey Minakin Lauren J Ayers Michael P Morley Apoorva Babu Carlos Villacorta-Martin Maria Yampolskaya Anne Hinds Bibek R Thapa Feiya Wang Adeline Matschulat Pankaj Mehta E Source Type: research

Nuclear RNA homeostasis promotes systems-level coordination of cell fate and senescence
Cell Stem Cell. 2024 Apr 12:S1934-5909(24)00096-1. doi: 10.1016/j.stem.2024.03.015. Online ahead of print.ABSTRACTUnderstanding cellular coordination remains a challenge despite knowledge of individual pathways. The RNA exosome, targeting a wide range of RNA substrates, is often downregulated in cellular senescence. Utilizing an auxin-inducible system, we observed that RNA exosome depletion in embryonic stem cells significantly affects the transcriptome and proteome, causing pluripotency loss and pre-senescence onset. Mechanistically, exosome depletion triggers acute nuclear RNA aggregation, disrupting nuclear RNA-protein ...
Source: Cell Stem Cell - April 17, 2024 Category: Stem Cells Authors: Xue Han Linqing Xing Yantao Hong Xuechun Zhang Bo Hao J Yuyang Lu Mengyuan Huang Zuhui Wang Shaoqian Ma Ge Zhan Tong Li Xiaowen Hao Yibing Tao Guanwen Li Shuqin Zhou Zheng Zheng Wen Shao Yitian Zeng Dacheng Ma Wenhao Zhang Zhen Xie Haiteng Deng Jiangwei Y Source Type: research

Nuclear RNA homeostasis promotes systems-level coordination of cell fate and senescence
Cell Stem Cell. 2024 Apr 12:S1934-5909(24)00096-1. doi: 10.1016/j.stem.2024.03.015. Online ahead of print.ABSTRACTUnderstanding cellular coordination remains a challenge despite knowledge of individual pathways. The RNA exosome, targeting a wide range of RNA substrates, is often downregulated in cellular senescence. Utilizing an auxin-inducible system, we observed that RNA exosome depletion in embryonic stem cells significantly affects the transcriptome and proteome, causing pluripotency loss and pre-senescence onset. Mechanistically, exosome depletion triggers acute nuclear RNA aggregation, disrupting nuclear RNA-protein ...
Source: Cell Stem Cell - April 17, 2024 Category: Stem Cells Authors: Xue Han Linqing Xing Yantao Hong Xuechun Zhang Bo Hao J Yuyang Lu Mengyuan Huang Zuhui Wang Shaoqian Ma Ge Zhan Tong Li Xiaowen Hao Yibing Tao Guanwen Li Shuqin Zhou Zheng Zheng Wen Shao Yitian Zeng Dacheng Ma Wenhao Zhang Zhen Xie Haiteng Deng Jiangwei Y Source Type: research

Osteopontin drives neuroinflammation and cell loss in MAPT-N279K frontotemporal dementia patient neurons
Cell Stem Cell. 2024 Apr 10:S1934-5909(24)00094-8. doi: 10.1016/j.stem.2024.03.013. Online ahead of print.ABSTRACTFrontotemporal dementia (FTD) is an incurable group of early-onset dementias that can be caused by the deposition of hyperphosphorylated tau in patient brains. However, the mechanisms leading to neurodegeneration remain largely unknown. Here, we combined single-cell analyses of FTD patient brains with a stem cell culture and transplantation model of FTD. We identified disease phenotypes in FTD neurons carrying the MAPT-N279K mutation, which were related to oxidative stress, oxidative phosphorylation, and neuroi...
Source: Cell Stem Cell - April 16, 2024 Category: Stem Cells Authors: Osama Al-Dalahmah Matti Lam Julie J McInvale Wenhui Qu Trang Nguyen Jeong-Yeon Mun Sam Kwon Nkechime Ifediora Aayushi Mahajan Nelson Humala Tristan Winters Ellen Angeles Kelly A Jakubiak Rebekka K ühn Yoon A Kim Maria Caterina De Rosa Claudia A Doege Fah Source Type: research

Parasympathetic neurons derived from human pluripotent stem cells model human diseases and development
Cell Stem Cell. 2024 Apr 4:S1934-5909(24)00092-4. doi: 10.1016/j.stem.2024.03.011. Online ahead of print.ABSTRACTAutonomic parasympathetic neurons (parasymNs) control unconscious body responses, including "rest-and-digest." ParasymN innervation is important for organ development, and parasymN dysfunction is a hallmark of autonomic neuropathy. However, parasymN function and dysfunction in humans are vastly understudied due to the lack of a model system. Human pluripotent stem cell (hPSC)-derived neurons can fill this void as a versatile platform. Here, we developed a differentiation paradigm detailing the derivation of func...
Source: Cell Stem Cell - April 12, 2024 Category: Stem Cells Authors: Hsueh-Fu Wu Kenyi Saito-Diaz Chia-Wei Huang Jessica L McAlpine Dong Eun Seo D Sumner Magruder Mohamed Ishan Harrison C Bergeron William H Delaney Fabio R Santori Smita Krishnaswamy Gerald W Hart Ya-Wen Chen Robert J Hogan Hong-Xiang Liu Natalia B Ivanova Source Type: research

Parasympathetic neurons derived from human pluripotent stem cells model human diseases and development
Cell Stem Cell. 2024 Apr 4:S1934-5909(24)00092-4. doi: 10.1016/j.stem.2024.03.011. Online ahead of print.ABSTRACTAutonomic parasympathetic neurons (parasymNs) control unconscious body responses, including "rest-and-digest." ParasymN innervation is important for organ development, and parasymN dysfunction is a hallmark of autonomic neuropathy. However, parasymN function and dysfunction in humans are vastly understudied due to the lack of a model system. Human pluripotent stem cell (hPSC)-derived neurons can fill this void as a versatile platform. Here, we developed a differentiation paradigm detailing the derivation of func...
Source: Cell Stem Cell - April 12, 2024 Category: Stem Cells Authors: Hsueh-Fu Wu Kenyi Saito-Diaz Chia-Wei Huang Jessica L McAlpine Dong Eun Seo D Sumner Magruder Mohamed Ishan Harrison C Bergeron William H Delaney Fabio R Santori Smita Krishnaswamy Gerald W Hart Ya-Wen Chen Robert J Hogan Hong-Xiang Liu Natalia B Ivanova Source Type: research

Parasympathetic neurons derived from human pluripotent stem cells model human diseases and development
Cell Stem Cell. 2024 Apr 4:S1934-5909(24)00092-4. doi: 10.1016/j.stem.2024.03.011. Online ahead of print.ABSTRACTAutonomic parasympathetic neurons (parasymNs) control unconscious body responses, including "rest-and-digest." ParasymN innervation is important for organ development, and parasymN dysfunction is a hallmark of autonomic neuropathy. However, parasymN function and dysfunction in humans are vastly understudied due to the lack of a model system. Human pluripotent stem cell (hPSC)-derived neurons can fill this void as a versatile platform. Here, we developed a differentiation paradigm detailing the derivation of func...
Source: Cell Stem Cell - April 12, 2024 Category: Stem Cells Authors: Hsueh-Fu Wu Kenyi Saito-Diaz Chia-Wei Huang Jessica L McAlpine Dong Eun Seo D Sumner Magruder Mohamed Ishan Harrison C Bergeron William H Delaney Fabio R Santori Smita Krishnaswamy Gerald W Hart Ya-Wen Chen Robert J Hogan Hong-Xiang Liu Natalia B Ivanova Source Type: research

Impact of CRISPR/HDR editing versus lentiviral transduction on long-term engraftment and clonal dynamics of HSPCs in rhesus macaques
Cell Stem Cell. 2024 Apr 9:S1934-5909(24)00132-2. doi: 10.1016/j.stem.2024.04.005. Online ahead of print.NO ABSTRACTPMID:38599215 | DOI:10.1016/j.stem.2024.04.005 (Source: Cell Stem Cell)
Source: Cell Stem Cell - April 10, 2024 Category: Stem Cells Authors: Byung-Chul Lee Ashley Gin Chuanfeng Wu Komudi Singh Max Grice Ryland Mortlock Diana Abraham Xing Fan Yifan Zhou Aisha AlJanahi Uimook Choi Suk See DeRavin Taehoon Shin Sogun Hong Cynthia E Dunbar Source Type: research

Impact of CRISPR/HDR editing versus lentiviral transduction on long-term engraftment and clonal dynamics of HSPCs in rhesus macaques
Cell Stem Cell. 2024 Apr 9:S1934-5909(24)00132-2. doi: 10.1016/j.stem.2024.04.005. Online ahead of print.NO ABSTRACTPMID:38599215 | DOI:10.1016/j.stem.2024.04.005 (Source: Cell Stem Cell)
Source: Cell Stem Cell - April 10, 2024 Category: Stem Cells Authors: Byung-Chul Lee Ashley Gin Chuanfeng Wu Komudi Singh Max Grice Ryland Mortlock Diana Abraham Xing Fan Yifan Zhou Aisha AlJanahi Uimook Choi Suk See DeRavin Taehoon Shin Sogun Hong Cynthia E Dunbar Source Type: research

Patient-derived tumor-like cell clusters for personalized chemo- and immunotherapies in non-small cell lung cancer
Cell Stem Cell. 2024 Apr 2:S1934-5909(24)00090-0. doi: 10.1016/j.stem.2024.03.008. Online ahead of print.ABSTRACTMany patient-derived tumor models have emerged recently. However, their potential to guide personalized drug selection remains unclear. Here, we report patient-derived tumor-like cell clusters (PTCs) for non-small cell lung cancer (NSCLC), capable of conducting 100-5,000 drug tests within 10 days. We have established 283 PTC models with an 81% success rate. PTCs contain primary tumor epithelium self-assembled with endogenous stromal and immune cells and show a high degree of similarity to the original tumors in ...
Source: Cell Stem Cell - April 9, 2024 Category: Stem Cells Authors: Shenyi Yin Ying Yu Nan Wu Minglei Zhuo Yanmin Wang Yanjie Niu Yiqian Ni Fang Hu Cuiming Ding Hongsheng Liu Xinghua Cheng Jin Peng Juan Li Yang He Jiaxin Li Junyi Wang Hanshuo Zhang Xiaoyu Zhai Bing Liu Yaqi Wang Shi Yan Mailin Chen Wenqing Li Jincui Peng Source Type: research

Rebuilding and rebooting immunity with stem cells
Cell Stem Cell. 2024 Apr 1:S1934-5909(24)00093-6. doi: 10.1016/j.stem.2024.03.012. Online ahead of print.ABSTRACTAdvances in modern medicine have enabled a rapid increase in lifespan and, consequently, have highlighted the immune system as a key driver of age-related disease. Immune regeneration therapies present exciting strategies to address age-related diseases by rebooting the host's primary lymphoid tissues or rebuilding the immune system directly via biomaterials or artificial tissue. Here, we identify important, unanswered questions regarding the safety and feasibility of these therapies. Further, we identify key de...
Source: Cell Stem Cell - April 9, 2024 Category: Stem Cells Authors: Laura N Stankiewicz Fabio M V Rossi Peter W Zandstra Source Type: research

Patient-derived tumor-like cell clusters for personalized chemo- and immunotherapies in non-small cell lung cancer
Cell Stem Cell. 2024 Apr 2:S1934-5909(24)00090-0. doi: 10.1016/j.stem.2024.03.008. Online ahead of print.ABSTRACTMany patient-derived tumor models have emerged recently. However, their potential to guide personalized drug selection remains unclear. Here, we report patient-derived tumor-like cell clusters (PTCs) for non-small cell lung cancer (NSCLC), capable of conducting 100-5,000 drug tests within 10 days. We have established 283 PTC models with an 81% success rate. PTCs contain primary tumor epithelium self-assembled with endogenous stromal and immune cells and show a high degree of similarity to the original tumors in ...
Source: Cell Stem Cell - April 9, 2024 Category: Stem Cells Authors: Shenyi Yin Ying Yu Nan Wu Minglei Zhuo Yanmin Wang Yanjie Niu Yiqian Ni Fang Hu Cuiming Ding Hongsheng Liu Xinghua Cheng Jin Peng Juan Li Yang He Jiaxin Li Junyi Wang Hanshuo Zhang Xiaoyu Zhai Bing Liu Yaqi Wang Shi Yan Mailin Chen Wenqing Li Jincui Peng Source Type: research

Rebuilding and rebooting immunity with stem cells
Cell Stem Cell. 2024 Apr 1:S1934-5909(24)00093-6. doi: 10.1016/j.stem.2024.03.012. Online ahead of print.ABSTRACTAdvances in modern medicine have enabled a rapid increase in lifespan and, consequently, have highlighted the immune system as a key driver of age-related disease. Immune regeneration therapies present exciting strategies to address age-related diseases by rebooting the host's primary lymphoid tissues or rebuilding the immune system directly via biomaterials or artificial tissue. Here, we identify important, unanswered questions regarding the safety and feasibility of these therapies. Further, we identify key de...
Source: Cell Stem Cell - April 9, 2024 Category: Stem Cells Authors: Laura N Stankiewicz Fabio M V Rossi Peter W Zandstra Source Type: research

Genetic haute couture to block HIV-1 at front doors
Cell Stem Cell. 2024 Apr 4;31(4):433-434. doi: 10.1016/j.stem.2024.03.009.ABSTRACTThe chemokine receptors CCR5 and CXCR4 are "front doors" for HIV-1 infection in host cells, and their targeting represents a potential solution for a cure. Dudek et al.1 now propose a new gene editing strategy to simultaneously block CCR5- and CXCR4-mediated HIV-1 entry in autologous hematopoietic stem and progenitor cells (HSPCs).PMID:38579679 | DOI:10.1016/j.stem.2024.03.009 (Source: Cell Stem Cell)
Source: Cell Stem Cell - April 5, 2024 Category: Stem Cells Authors: Petronela Ancuta Source Type: research