Stem Cell Reports最新文献_第10页

The histone acetyltransferase KAT6B is required for hematopoietic stem cell development and function. 组蛋白乙酰转移酶KAT6B是造血干细胞发育和功能所必需的。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-04-09 Epub Date: 2024-03-21 DOI: 10.1016/j.stemcr.2024.02.005

Maria I Bergamasco, Nishika Ranathunga, Waruni Abeysekera, Connie S N Li-Wai-Suen, Alexandra L Garnham, Simon N Willis, Helen M McRae, Yuqing Yang, Angela D'Amico, Ladina Di Rago, Stephen Wilcox, Stephen L Nutt, Warren S Alexander, Gordon K Smyth, Anne K Voss, Tim Thomas

{"title":"The histone acetyltransferase KAT6B is required for hematopoietic stem cell development and function.","authors":"Maria I Bergamasco, Nishika Ranathunga, Waruni Abeysekera, Connie S N Li-Wai-Suen, Alexandra L Garnham, Simon N Willis, Helen M McRae, Yuqing Yang, Angela D'Amico, Ladina Di Rago, Stephen Wilcox, Stephen L Nutt, Warren S Alexander, Gordon K Smyth, Anne K Voss, Tim Thomas","doi":"10.1016/j.stemcr.2024.02.005","DOIUrl":"10.1016/j.stemcr.2024.02.005","url":null,"abstract":"The histone lysine acetyltransferase KAT6B (MYST4, MORF, QKF) is the target of recurrent chromosomal translocations causing hematological malignancies with poor prognosis. Using Kat6b germline deletion and overexpression in mice, we determined the role of KAT6B in the hematopoietic system. We found that KAT6B sustained the fetal hematopoietic stem cell pool but did not affect viability or differentiation. KAT6B was essential for normal levels of histone H3 lysine 9 (H3K9) acetylation but not for a previously proposed target, H3K23. Compound heterozygosity of Kat6b and the closely related gene, Kat6a, abolished hematopoietic reconstitution after transplantation. KAT6B and KAT6A cooperatively promoted transcription of genes regulating hematopoiesis, including the Hoxa cluster, Pbx1, Meis1, Gata family, Erg, and Flt3. In conclusion, we identified the hematopoietic processes requiring Kat6b and showed that KAT6B and KAT6A synergistically promoted HSC development, function, and transcription. Our findings are pertinent to current clinical trials testing KAT6A/B inhibitors as cancer therapeutics.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"469-485"},"PeriodicalIF":5.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MST1/2 regulates fibro/adipogenic progenitor fate decisions in skeletal muscle regeneration. MST1/2调节骨骼肌再生过程中纤维/脂肪生成祖细胞命运的决定。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-04-09 Epub Date: 2024-03-28 DOI: 10.1016/j.stemcr.2024.02.010

Kezhi Wang, Jingjing Yang, Yina An, Jing Wang, Shuyu Tan, Hui Xu, Yanjun Dong

{"title":"MST1/2 regulates fibro/adipogenic progenitor fate decisions in skeletal muscle regeneration.","authors":"Kezhi Wang, Jingjing Yang, Yina An, Jing Wang, Shuyu Tan, Hui Xu, Yanjun Dong","doi":"10.1016/j.stemcr.2024.02.010","DOIUrl":"10.1016/j.stemcr.2024.02.010","url":null,"abstract":"Defective skeletal muscle regeneration is often accompanied by fibrosis. Fibroblast/adipose progenitors (FAPs) are important in these processes, however, the regulation of FAP fate decisions is unclear. Here, using inducible conditional knockout mice, we show that blocking mammalian Ste20-like kinases 1/2 (MST1/2) of FAPs prevented apoptosis and reduced interleukin-6 secretion in vivo and in vitro, which impaired myoblast proliferation and differentiation, as well as impaired muscle regeneration. Deletion of Mst1/2 increased co-localization of Yes-associated protein (YAP) with Smad2/3 in nuclei and promoted differentiation of FAPs toward myofibroblasts, resulting in excessive collagen deposition and skeletal muscle fibrosis. Meanwhile, inhibition of MST1/2 increased YAP/Transcriptional co-activator with PDZ-binding motif activation, which promoted activation of the WNT/β-catenin pathway and impaired the differentiation of FAPs toward adipocytes. These results reveal a new mechanism for MST1/2 action in disrupted skeletal muscle regeneration and fibrosis via regulation of FAP apoptosis and differentiation. MST1/2 is a potential therapeutic target for the treatment of some myopathies.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"501-514"},"PeriodicalIF":5.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140327180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SARS-CoV-2 tropism to intestinal but not gastric epithelial cells is defined by limited ACE2 expression SARS-CoV-2 对肠道上皮细胞而非胃上皮细胞的滋养是由 ACE2 的有限表达决定的

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-04-01 DOI: 10.1016/j.stemcr.2024.03.008

Mindaugas Paužuolis, D. Fatykhova, Boris Zühlke, Torsten Schwecke, Mastura Neyazi, Pilar Samperio-Ventayol, Carmen Aguilar, Nicolas Schlegel, Simon Dökel, Markus Ralser, Andreas Hocke, Christine Krempl, Sina Bartfeld

引用次数: 0

Survivors of polymicrobial sepsis are refractory to G-CSF-induced emergency myelopoiesis and hematopoietic stem and progenitor cell mobilization. 多微生物败血症幸存者对G-CSF诱导的紧急骨髓造血和造血干细胞及祖细胞动员无效。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-04-01 DOI: 10.1016/j.stemcr.2024.03.007

Nirupam Biswas, Amber Bahr, Jennifer Howard, Jesse L. Bonin, Rachel Grazda, Katherine C. MacNamara

引用次数: 0

Recommendations on fit-for-purpose criteria to establish quality management for microphysiological systems and for monitoring their reproducibility 关于建立微观生理系统质量管理和监测其再现性的适用标准的建议

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-04-01 DOI: 10.1016/j.stemcr.2024.03.009

David Pamies, Jason Ekert, M. Zurich, Olivier Frey, Sophie Werner, Monica Piergiovanni, Benjamin S. Freedman, Adrian Kee Keong Teo, Hendrik Erfurth, Darwin R. Reyes, Peter Loskill, Pelin Candarlioglu, Laura Suter-Dick, Shan Wang, Thomas Hartung, Sandra Coecke, Glyn Stacey, Beren Atac Wagegg, Eva-Maria Dehne, Francesca Pistollato, Marcel Leist

引用次数: 0

Human-induced pluripotent stem cell-derived neural stem/progenitor cell ex vivo gene therapy with synaptic organizer CPTX for spinal cord injury. 用突触组织者CPTX进行脊髓损伤的人诱导多能干细胞衍生神经干/祖细胞体外基因治疗。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-03-12 Epub Date: 2024-02-15 DOI: 10.1016/j.stemcr.2024.01.007

Yusuke Saijo, Narihito Nagoshi, Momotaro Kawai, Takahiro Kitagawa, Yu Suematsu, Masahiro Ozaki, Munehisa Shinozaki, Jun Kohyama, Shinsuke Shibata, Kosei Takeuchi, Masaya Nakamura, Michisuke Yuzaki, Hideyuki Okano

{"title":"Human-induced pluripotent stem cell-derived neural stem/progenitor cell ex vivo gene therapy with synaptic organizer CPTX for spinal cord injury.","authors":"Yusuke Saijo, Narihito Nagoshi, Momotaro Kawai, Takahiro Kitagawa, Yu Suematsu, Masahiro Ozaki, Munehisa Shinozaki, Jun Kohyama, Shinsuke Shibata, Kosei Takeuchi, Masaya Nakamura, Michisuke Yuzaki, Hideyuki Okano","doi":"10.1016/j.stemcr.2024.01.007","DOIUrl":"10.1016/j.stemcr.2024.01.007","url":null,"abstract":"The transplantation of neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) has shown promise in spinal cord injury (SCI) model animals. Establishing a functional synaptic connection between the transplanted and host neurons is crucial for motor function recovery. To boost therapeutic outcomes, we developed an ex vivo gene therapy aimed at promoting synapse formation by expressing the synthetic excitatory synapse organizer CPTX in hiPSC-NS/PCs. Using an immunocompromised transgenic rat model of SCI, we evaluated the effects of transplanting CPTX-expressing hiPSC-NS/PCs using histological and functional analyses. Our findings revealed a significant increase in excitatory synapse formation at the transplantation site. Retrograde monosynaptic tracing indicated extensive integration of transplanted neurons into the surrounding neuronal tracts facilitated by CPTX. Consequently, locomotion and spinal cord conduction significantly improved. Thus, ex vivo gene therapy targeting synapse formation holds promise for future clinical applications and offers potential benefits to individuals with SCI.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"383-398"},"PeriodicalIF":5.9,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10937157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MSX1⁺PDGFRA^low limb mesenchyme-like cells as an efficient stem cell source for human cartilage regeneration. MSX1+PDGFRA-low肢体间充质样细胞是人类软骨再生的高效干细胞来源。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-03-12 Epub Date: 2024-02-29 DOI: 10.1016/j.stemcr.2024.02.001

Yuansong Liao, Fanchen Kang, Jingfei Xiong, Kun Xie, Mingxu Li, Ling Yu, Yuqing Wang, Hanyi Chen, Guogen Ye, Yike Yin, Weihua Guo, Haoyang Cai, Qing Zhu, Zhonghan Li

{"title":"MSX1+PDGFRAlow limb mesenchyme-like cells as an efficient stem cell source for human cartilage regeneration.","authors":"Yuansong Liao, Fanchen Kang, Jingfei Xiong, Kun Xie, Mingxu Li, Ling Yu, Yuqing Wang, Hanyi Chen, Guogen Ye, Yike Yin, Weihua Guo, Haoyang Cai, Qing Zhu, Zhonghan Li","doi":"10.1016/j.stemcr.2024.02.001","DOIUrl":"10.1016/j.stemcr.2024.02.001","url":null,"abstract":"Degenerative bone disorders have a significant impact on global health, and regeneration of articular cartilage remains a challenge. Existing cell therapies using mesenchymal stromal cells (MSCs) have shown limited efficacy, highlighting the necessity for alternative stem cell sources. Here, we have identified and characterized MSX1+ mesenchymal progenitor cells in the developing limb bud with remarkable osteochondral-regenerative and microenvironment-adaptive capabilities. Single-cell sequencing further revealed the presence of two major cell compositions within the MSX1+ cells, where a distinct PDGFRAlow subset retained the strongest osteochondral competency and could efficiently regenerate articular cartilage in vivo. Furthermore, a strategy was developed to generate MSX1+PDGFRAlow limb mesenchyme-like (LML) cells from human pluripotent stem cells that closely resembled their mouse counterparts, which were bipotential in vitro and could directly regenerate damaged cartilage in a mouse injury model. Together, our results indicated that MSX1+PDGFRAlow LML cells might be a prominent stem cell source for human cartilage regeneration.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"399-413"},"PeriodicalIF":5.9,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10937155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-03-12 Epub Date: 2024-02-08 DOI: 10.1016/j.stemcr.2024.01.002

Jacob A Klickstein, Michelle A Johnson, Pantelis Antonoudiou, Jamie Maguire, Joao A Paulo, Steve P Gygi, Chris Weihl, Malavika Raman

{"title":"ALS-related p97 R155H mutation disrupts lysophagy in iPSC-derived motor neurons.","authors":"Jacob A Klickstein, Michelle A Johnson, Pantelis Antonoudiou, Jamie Maguire, Joao A Paulo, Steve P Gygi, Chris Weihl, Malavika Raman","doi":"10.1016/j.stemcr.2024.01.002","DOIUrl":"10.1016/j.stemcr.2024.01.002","url":null,"abstract":"Mutations in the AAA+ ATPase p97 cause multisystem proteinopathy 1, which includes amyotrophic lateral sclerosis; however, the pathogenic mechanisms that contribute to motor neuron loss remain obscure. Here, we use two induced pluripotent stem cell models differentiated into spinal motor neurons to investigate how p97 mutations perturb the motor neuron proteome. Using quantitative proteomics, we find that motor neurons harboring the p97 R155H mutation have deficits in the selective autophagy of lysosomes (lysophagy). p97 R155H motor neurons are unable to clear damaged lysosomes and have reduced viability. Lysosomes in mutant motor neurons have increased pH compared with wild-type cells. The clearance of damaged lysosomes involves UBXD1-p97 interaction, which is disrupted in mutant motor neurons. Finally, inhibition of the ATPase activity of p97 using the inhibitor CB-5083 rescues lysophagy defects in mutant motor neurons. These results add to the evidence that endo-lysosomal dysfunction is a key aspect of disease pathogenesis in p97-related disorders.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"366-382"},"PeriodicalIF":5.9,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10937112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Growth/differentiation factor 15 controls ependymal and stem cell number in the V-SVZ. 生长/分化因子15控制着V-SVZ的上皮细胞和干细胞数量。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-03-12 Epub Date: 2024-02-15 DOI: 10.1016/j.stemcr.2024.01.008

Katja Baur, Carmen Carrillo-García, Şeydanur Şan, Manja von Hahn, Jens Strelau, Gabriele Hölzl-Wenig, Claudia Mandl, Francesca Ciccolini

{"title":"Growth/differentiation factor 15 controls ependymal and stem cell number in the V-SVZ.","authors":"Katja Baur, Carmen Carrillo-García, Şeydanur Şan, Manja von Hahn, Jens Strelau, Gabriele Hölzl-Wenig, Claudia Mandl, Francesca Ciccolini","doi":"10.1016/j.stemcr.2024.01.008","DOIUrl":"10.1016/j.stemcr.2024.01.008","url":null,"abstract":"The expression of growth/differentiation factor (GDF) 15 increases in the ganglionic eminence (GE) late in neural development, especially in neural stem cells (NSCs). However, GDF15 function in this region remains unknown. We report that GDF15 receptor is expressed apically in the GE and that GDF15 ablation promotes proliferation and cell division in the embryonic GE and in the adult ventricular-subventricular zone (V-SVZ). This causes a transient generation of additional neuronal progenitors, compensated by cell death, and a lasting increase in the number of ependymal cells and apical NSCs. Finally, both GDF15 receptor and the epidermal growth factor receptor (EGFR) were expressed in progenitors and mutation of GDF15 affected EGFR signaling. However, only exposure to exogenous GDF15, but not to EGF, normalized proliferation and the number of apical progenitors. Thus, GDF15 regulates proliferation of apical progenitors in the GE, thereby affecting the number of ependymal cells and NSCs.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"351-365"},"PeriodicalIF":5.9,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10937156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ER stress and lipid imbalance drive diabetic embryonic cardiomyopathy in an organoid model of human heart development. ER应激和脂质失衡驱动类器官人体心脏发育模型中的糖尿病胚胎心肌病。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-03-12 Epub Date: 2024-02-08 DOI: 10.1016/j.stemcr.2024.01.003

Aleksandra Kostina, Yonatan R Lewis-Israeli, Mishref Abdelhamid, Mitchell A Gabalski, Artem Kiselev, Brett D Volmert, Haley Lankerd, Amanda R Huang, Aaron H Wasserman, Todd Lydic, Christina Chan, Sangbum Park, Isoken Olomu, Aitor Aguirre

{"title":"ER stress and lipid imbalance drive diabetic embryonic cardiomyopathy in an organoid model of human heart development.","authors":"Aleksandra Kostina, Yonatan R Lewis-Israeli, Mishref Abdelhamid, Mitchell A Gabalski, Artem Kiselev, Brett D Volmert, Haley Lankerd, Amanda R Huang, Aaron H Wasserman, Todd Lydic, Christina Chan, Sangbum Park, Isoken Olomu, Aitor Aguirre","doi":"10.1016/j.stemcr.2024.01.003","DOIUrl":"10.1016/j.stemcr.2024.01.003","url":null,"abstract":"Congenital heart defects are the most prevalent human birth defects, and their incidence is exacerbated by maternal health conditions, such as diabetes during the first trimester (pregestational diabetes). Our understanding of the pathology of these disorders is hindered by a lack of human models and the inaccessibility of embryonic tissue. Using an advanced human heart organoid system, we simulated embryonic heart development under pregestational diabetes-like conditions. These organoids developed pathophysiological features observed in mouse and human studies before, including ROS-mediated stress and cardiomyocyte hypertrophy. scRNA-seq revealed cardiac cell-type-specific dysfunction affecting epicardial and cardiomyocyte populations and alterations in the endoplasmic reticulum and very-long-chain fatty acid lipid metabolism. Imaging and lipidomics confirmed these findings and showed that dyslipidemia was linked to fatty acid desaturase 2 mRNA decay dependent on IRE1-RIDD signaling. Targeting IRE1 or restoring lipid levels partially reversed the effects of pregestational diabetes, offering potential preventive and therapeutic strategies in humans.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"317-330"},"PeriodicalIF":5.9,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10937107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0