Cell stem cell最新文献_第4页

SRCAP mutations drive clonal hematopoiesis through epigenetic and DNA repair dysregulation. SRCAP突变通过表观遗传学和DNA修复失调驱动克隆性造血。

Cell stem cell Pub Date : 2023-11-02 Epub Date: 2023-10-19 DOI: 10.1016/j.stem.2023.09.011

Chun-Wei Chen, Linda Zhang, Ravi Dutta, Abhishek Niroula, Peter G Miller, Christopher J Gibson, Alexander G Bick, Jaime M Reyes, Yi-Tang Lee, Ayala Tovy, Tianpeng Gu, Sarah Waldvogel, Yi-Hung Chen, Bryan J Venters, Pierre-Olivier Estève, Sriharsa Pradhan, Michael-Christopher Keogh, Pradeep Natarajan, Koichi Takahashi, Adam S Sperling, Margaret A Goodell

{"title":"SRCAP mutations drive clonal hematopoiesis through epigenetic and DNA repair dysregulation.","authors":"Chun-Wei Chen, Linda Zhang, Ravi Dutta, Abhishek Niroula, Peter G Miller, Christopher J Gibson, Alexander G Bick, Jaime M Reyes, Yi-Tang Lee, Ayala Tovy, Tianpeng Gu, Sarah Waldvogel, Yi-Hung Chen, Bryan J Venters, Pierre-Olivier Estève, Sriharsa Pradhan, Michael-Christopher Keogh, Pradeep Natarajan, Koichi Takahashi, Adam S Sperling, Margaret A Goodell","doi":"10.1016/j.stem.2023.09.011","DOIUrl":"10.1016/j.stem.2023.09.011","url":null,"abstract":"Somatic mutations accumulate in all cells with age and can confer a selective advantage, leading to clonal expansion over time. In hematopoietic cells, mutations in a subset of genes regulating DNA repair or epigenetics frequently lead to clonal hematopoiesis (CH). Here, we describe the context and mechanisms that lead to enrichment of hematopoietic stem cells (HSCs) with mutations in SRCAP, which encodes a chromatin remodeler that also influences DNA repair. We show that SRCAP mutations confer a selective advantage in human cells and in mice upon treatment with the anthracycline-class chemotherapeutic doxorubicin and bone marrow transplantation. Furthermore, Srcap mutations lead to a lymphoid-biased expansion, driven by loss of SRCAP-regulated H2A.Z deposition and increased DNA repair. Altogether, we demonstrate that SRCAP operates at the intersection of multiple pathways in stem and progenitor cells, offering a new perspective on the functional impact of genetic variants that promote stem cell competition in the hematopoietic system.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"1503-1519.e8"},"PeriodicalIF":0.0,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10841682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49686269","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

Hematopoietic stem cells through the ages: A lifetime of adaptation to organismal demands. 长年累月的造血干细胞：终生适应生物体需求。

Cell stem cell Pub Date : 2023-11-02 Epub Date: 2023-10-20 DOI: 10.1016/j.stem.2023.09.013

Monica Kasbekar, Carl A Mitchell, Melissa A Proven, Emmanuelle Passegué

引用次数: 0

Skull progenitor cell-driven meningeal lymphatic restoration improves neurocognitive functions in craniosynostosis. 颅骨祖细胞驱动的脑膜淋巴修复可改善颅缝闭合症的神经认知功能。

Cell stem cell Pub Date : 2023-11-02 Epub Date: 2023-10-19 DOI: 10.1016/j.stem.2023.09.012

Li Ma, Qing Chang, Fei Pei, Mengmeng Liu, Wei Zhang, Young-Kwon Hong, Yang Chai, Jian-Fu Chen

{"title":"Skull progenitor cell-driven meningeal lymphatic restoration improves neurocognitive functions in craniosynostosis.","authors":"Li Ma, Qing Chang, Fei Pei, Mengmeng Liu, Wei Zhang, Young-Kwon Hong, Yang Chai, Jian-Fu Chen","doi":"10.1016/j.stem.2023.09.012","DOIUrl":"10.1016/j.stem.2023.09.012","url":null,"abstract":"The meninges lie in the interface between the skull and brain, harboring lymphatic vasculature and skull progenitor cells (SPCs). How the skull and brain communicate remains largely unknown. We found that impaired meningeal lymphatics and brain perfusion drive neurocognitive defects in Twist1+/- mice, an animal model of craniosynostosis recapitulating human Saethre-Chotzen syndrome. Loss of SPCs leads to skull deformities and elevated intracranial pressure (ICP), whereas transplanting SPCs back into mutant mice mitigates lymphatic and brain defects through two mechanisms: (1) decreasing elevated ICP by skull correction and (2) promoting the growth and migration of lymphatic endothelial cells (LECs) via SPC-secreted vascular endothelial growth factor-C (VEGF-C). Treating Twist1+/- mice with VEGF-C promotes meningeal lymphatic growth and rescues defects in ICP, brain perfusion, and neurocognitive functions. Thus, the skull functionally integrates with the brain via meningeal lymphatics, which is impaired in craniosynostosis and can be restored by SPC-driven lymphatic activation via VEGF-C.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"1472-1485.e7"},"PeriodicalIF":0.0,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10842404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49686268","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

Spatial-temporal proliferation of hepatocytes during pregnancy revealed by genetic lineage tracing. 遗传谱系追踪揭示妊娠期肝细胞的时空增殖。

Cell stem cell Pub Date : 2023-11-02 Epub Date: 2023-10-03 DOI: 10.1016/j.stem.2023.09.002

Shun He, Zhihou Guo, Mingshan Zhou, Haichang Wang, Zhuonan Zhang, Mengyang Shi, Xufeng Li, Xueying Yang, Lingjuan He

{"title":"Spatial-temporal proliferation of hepatocytes during pregnancy revealed by genetic lineage tracing.","authors":"Shun He, Zhihou Guo, Mingshan Zhou, Haichang Wang, Zhuonan Zhang, Mengyang Shi, Xufeng Li, Xueying Yang, Lingjuan He","doi":"10.1016/j.stem.2023.09.002","DOIUrl":"10.1016/j.stem.2023.09.002","url":null,"abstract":"The maternal liver undergoes dramatic enlargement to adapt to the increased metabolic demands during pregnancy. However, the cellular sources for liver growth during pregnancy remain largely elusive. Here, we employed a proliferation recording system, ProTracer, to examine the spatial-temporal proliferation of hepatocytes during pregnancy. We discovered that during early to late pregnancy, hepatocyte proliferation initiated from zone 1, to zone 2, and lastly to zone 3, with the majority of new hepatocytes being generated in zone 2. Additionally, using single-cell RNA sequencing, we observed that Ccnd1 was highly enriched in zone 2 hepatocytes. We further applied dual-recombinase-mediated genetic lineage tracing to reveal that Ccnd1+ hepatocytes expanded preferentially during pregnancy. Moreover, we demonstrated that estrogen induces liver enlargement during pregnancy, which was abolished in Ccnd1 knockout mice. Our work revealed a unique spatial-temporal hepatocyte proliferation pattern during pregnancy, with Ccnd1+ hepatocytes in zone 2 serving as the major cellular source for hepatic enlargement.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"1549-1558.e5"},"PeriodicalIF":0.0,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41143277","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

Genome-wide CRISPR activation screening in senescent cells reveals SOX5 as a driver and therapeutic target of rejuvenation. 衰老细胞中的全基因组CRISPR激活筛选揭示了SOX5是年轻化的驱动因素和治疗靶点。

Cell stem cell Pub Date : 2023-11-02 Epub Date: 2023-10-12 DOI: 10.1016/j.stem.2023.09.007

Yaobin Jing, Xiaoyu Jiang, Qianzhao Ji, Zeming Wu, Wei Wang, Zunpeng Liu, Pedro Guillen-Garcia, Concepcion Rodriguez Esteban, Pradeep Reddy, Steve Horvath, Jingyi Li, Lingling Geng, Qinchao Hu, Si Wang, Juan Carlos Izpisua Belmonte, Jie Ren, Weiqi Zhang, Jing Qu, Guang-Hui Liu

{"title":"Genome-wide CRISPR activation screening in senescent cells reveals SOX5 as a driver and therapeutic target of rejuvenation.","authors":"Yaobin Jing, Xiaoyu Jiang, Qianzhao Ji, Zeming Wu, Wei Wang, Zunpeng Liu, Pedro Guillen-Garcia, Concepcion Rodriguez Esteban, Pradeep Reddy, Steve Horvath, Jingyi Li, Lingling Geng, Qinchao Hu, Si Wang, Juan Carlos Izpisua Belmonte, Jie Ren, Weiqi Zhang, Jing Qu, Guang-Hui Liu","doi":"10.1016/j.stem.2023.09.007","DOIUrl":"10.1016/j.stem.2023.09.007","url":null,"abstract":"Our understanding of the molecular basis for cellular senescence remains incomplete, limiting the development of strategies to ameliorate age-related pathologies by preventing stem cell senescence. Here, we performed a genome-wide CRISPR activation (CRISPRa) screening using a human mesenchymal precursor cell (hMPC) model of the progeroid syndrome. We evaluated targets whose activation antagonizes cellular senescence, among which SOX5 outperformed as a top hit. Through decoding the epigenomic landscapes remodeled by overexpressing SOX5, we uncovered its role in resetting the transcription network for geroprotective genes, including HMGB2. Mechanistically, SOX5 binding elevated the enhancer activity of HMGB2 with increased levels of H3K27ac and H3K4me1, raising HMGB2 expression so as to promote rejuvenation. Furthermore, gene therapy with lentiviruses carrying SOX5 or HMGB2 rejuvenated cartilage and alleviated osteoarthritis in aged mice. Our study generated a comprehensive list of rejuvenators, pinpointing SOX5 as a potent driver for rejuvenation both in vitro and in vivo.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"1452-1471.e10"},"PeriodicalIF":0.0,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41223577","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

Human pallial MGE-type GABAergic interneuron cell therapy for chronic focal epilepsy. 人大脑皮层MGE型GABA能中间神经元细胞治疗慢性局灶性癫痫。

Cell stem cell Pub Date : 2023-10-05 DOI: 10.1016/j.stem.2023.08.013

Marina Bershteyn, Sonja Bröer, Mansi Parekh, Yves Maury, Steven Havlicek, Sonja Kriks, Luis Fuentealba, Seonok Lee, Robin Zhou, Geetha Subramanyam, Meliz Sezan, Eric Steven Sevilla, Whitney Blankenberger, Julien Spatazza, Li Zhou, Hubert Nethercott, David Traver, Philip Hampel, Hannah Kim, Michael Watson, Naomi Salter, Anastasia Nesterova, Wai Au, Arnold Kriegstein, Arturo Alvarez-Buylla, John Rubenstein, Gautam Banik, Alessandro Bulfone, Catherine Priest, Cory R Nicholas

{"title":"Human pallial MGE-type GABAergic interneuron cell therapy for chronic focal epilepsy.","authors":"Marina Bershteyn, Sonja Bröer, Mansi Parekh, Yves Maury, Steven Havlicek, Sonja Kriks, Luis Fuentealba, Seonok Lee, Robin Zhou, Geetha Subramanyam, Meliz Sezan, Eric Steven Sevilla, Whitney Blankenberger, Julien Spatazza, Li Zhou, Hubert Nethercott, David Traver, Philip Hampel, Hannah Kim, Michael Watson, Naomi Salter, Anastasia Nesterova, Wai Au, Arnold Kriegstein, Arturo Alvarez-Buylla, John Rubenstein, Gautam Banik, Alessandro Bulfone, Catherine Priest, Cory R Nicholas","doi":"10.1016/j.stem.2023.08.013","DOIUrl":"10.1016/j.stem.2023.08.013","url":null,"abstract":"Mesial temporal lobe epilepsy (MTLE) is the most common focal epilepsy. One-third of patients have drug-refractory seizures and are left with suboptimal therapeutic options such as brain tissue-destructive surgery. Here, we report the development and characterization of a cell therapy alternative for drug-resistant MTLE, which is derived from a human embryonic stem cell line and comprises cryopreserved, post-mitotic, medial ganglionic eminence (MGE) pallial-type GABAergic interneurons. Single-dose intrahippocampal delivery of the interneurons in a mouse model of chronic MTLE resulted in consistent mesiotemporal seizure suppression, with most animals becoming seizure-free and surviving longer. The grafted interneurons dispersed locally, functionally integrated, persisted long term, and significantly reduced dentate granule cell dispersion, a pathological hallmark of MTLE. These disease-modifying effects were dose-dependent, with a broad therapeutic range. No adverse effects were observed. These findings support an ongoing phase 1/2 clinical trial (NCT05135091) for drug-resistant MTLE.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":"30 10","pages":"1331-1350.e11"},"PeriodicalIF":0.0,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10993865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41175368","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

The variability of judicial decisions in the stem cell industry in China. 中国干细胞行业司法判决的可变性。

Cell stem cell Pub Date : 2023-10-05 DOI: 10.1016/j.stem.2023.09.005

Luxia Chen, Jianchao Gao, Ruohan Feng, Yaojin Peng

引用次数: 0

Complement factor D targeting protects endotheliopathy in organoid and monkey models of COVID-19. 补体因子D靶向保护新冠肺炎类器官和猴子模型中的内皮病变。

Cell stem cell Pub Date : 2023-10-05 DOI: 10.1016/j.stem.2023.09.001

Eri Kawakami, Norikazu Saiki, Yosuke Yoneyama, Chiharu Moriya, Mari Maezawa, Shuntaro Kawamura, Akiko Kinebuchi, Tamaki Kono, Masaaki Funata, Ayaka Sakoda, Shigeru Kondo, Takeshi Ebihara, Hisatake Matsumoto, Yuki Togami, Hiroshi Ogura, Fuminori Sugihara, Daisuke Okuzaki, Takashi Kojima, Sayaka Deguchi, Sebastien Vallee, Susan McQuade, Rizwana Islam, Madhusudan Natarajan, Hirohito Ishigaki, Misako Nakayama, Cong Thanh Nguyen, Yoshinori Kitagawa, Yunheng Wu, Kensaku Mori, Takayuki Hishiki, Tomohiko Takasaki, Yasushi Itoh, Kazuo Takayama, Yasunori Nio, Takanori Takebe

{"title":"Complement factor D targeting protects endotheliopathy in organoid and monkey models of COVID-19.","authors":"Eri Kawakami, Norikazu Saiki, Yosuke Yoneyama, Chiharu Moriya, Mari Maezawa, Shuntaro Kawamura, Akiko Kinebuchi, Tamaki Kono, Masaaki Funata, Ayaka Sakoda, Shigeru Kondo, Takeshi Ebihara, Hisatake Matsumoto, Yuki Togami, Hiroshi Ogura, Fuminori Sugihara, Daisuke Okuzaki, Takashi Kojima, Sayaka Deguchi, Sebastien Vallee, Susan McQuade, Rizwana Islam, Madhusudan Natarajan, Hirohito Ishigaki, Misako Nakayama, Cong Thanh Nguyen, Yoshinori Kitagawa, Yunheng Wu, Kensaku Mori, Takayuki Hishiki, Tomohiko Takasaki, Yasushi Itoh, Kazuo Takayama, Yasunori Nio, Takanori Takebe","doi":"10.1016/j.stem.2023.09.001","DOIUrl":"10.1016/j.stem.2023.09.001","url":null,"abstract":"COVID-19 is linked to endotheliopathy and coagulopathy, which can result in multi-organ failure. The mechanisms causing endothelial damage due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain elusive. Here, we developed an infection-competent human vascular organoid from pluripotent stem cells for modeling endotheliopathy. Longitudinal serum proteome analysis identified aberrant complement signature in critically ill patients driven by the amplification cycle regulated by complement factor B and D (CFD). This deviant complement pattern initiates endothelial damage, neutrophil activation, and thrombosis specific to organoid-derived human blood vessels, as verified through intravital imaging. We examined a new long-acting, pH-sensitive (acid-switched) antibody targeting CFD. In both human and macaque COVID-19 models, this long-acting anti-CFD monoclonal antibody mitigated abnormal complement activation, protected endothelial cells, and curtailed the innate immune response post-viral exposure. Collectively, our findings suggest that the complement alternative pathway exacerbates endothelial injury and inflammation. This underscores the potential of CFD-targeted therapeutics against severe viral-induced inflammathrombotic outcomes.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":"30 10","pages":"1315-1330.e10"},"PeriodicalIF":0.0,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10575686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41108021","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

Seizing hope: Advancing cell therapy for pharmaco-resistant epilepsy toward the clinic. 抓住希望：将耐药癫痫的细胞治疗推向临床。

Cell stem cell Pub Date : 2023-10-05 DOI: 10.1016/j.stem.2023.08.006

Ana Beltrán Arranz, Benedikt Berninger

引用次数: 0

Tissue morphology influences the temporal program of human brain organoid development. 组织形态学影响人类大脑类器官发育的时间程序。

Cell stem cell Pub Date : 2023-10-05 DOI: 10.1016/j.stem.2023.09.003

Ilaria Chiaradia, Ivan Imaz-Rosshandler, Benedikt S Nilges, Jerome Boulanger, Laura Pellegrini, Richa Das, Nachiket D Kashikar, Madeline A Lancaster

{"title":"Tissue morphology influences the temporal program of human brain organoid development.","authors":"Ilaria Chiaradia, Ivan Imaz-Rosshandler, Benedikt S Nilges, Jerome Boulanger, Laura Pellegrini, Richa Das, Nachiket D Kashikar, Madeline A Lancaster","doi":"10.1016/j.stem.2023.09.003","DOIUrl":"10.1016/j.stem.2023.09.003","url":null,"abstract":"Progression through fate decisions determines cellular composition and tissue architecture, but how that same architecture may impact cell fate is less clear. We took advantage of organoids as a tractable model to interrogate this interaction of form and fate. Screening methodological variations revealed that common protocol adjustments impacted various aspects of morphology, from macrostructure to tissue architecture. We examined the impact of morphological perturbations on cell fate through integrated single nuclear RNA sequencing (snRNA-seq) and spatial transcriptomics. Regardless of the specific protocol, organoids with more complex morphology better mimicked in vivo human fetal brain development. Organoids with perturbed tissue architecture displayed aberrant temporal progression, with cells being intermingled in both space and time. Finally, encapsulation to impart a simplified morphology led to disrupted tissue cytoarchitecture and a similar abnormal maturational timing. These data demonstrate that cells of the developing brain require proper spatial coordinates to undergo correct temporal progression.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":"30 10","pages":"1351-1367.e10"},"PeriodicalIF":0.0,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10765088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41179898","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