Stem Cell Reports最新文献_第7页

The lung microvasculature promotes alveolar type 2 cell differentiation via secreted SPARCL1. 肺微血管通过分泌SPARCL1促进肺泡2型细胞分化。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-04-08 Epub Date: 2025-03-20 DOI: 10.1016/j.stemcr.2025.102451

Paolo Panza, Hyun-Taek Kim, Till Lautenschläger, Janett Piesker, Stefan Günther, Yousef Alayoubi, Ondine Cleaver, Mario Looso, Didier Y R Stainier

{"title":"The lung microvasculature promotes alveolar type 2 cell differentiation via secreted SPARCL1.","authors":"Paolo Panza, Hyun-Taek Kim, Till Lautenschläger, Janett Piesker, Stefan Günther, Yousef Alayoubi, Ondine Cleaver, Mario Looso, Didier Y R Stainier","doi":"10.1016/j.stemcr.2025.102451","DOIUrl":"10.1016/j.stemcr.2025.102451","url":null,"abstract":"Lung endothelial cells (ECs) and pericytes are closely juxtaposed with the respiratory epithelium before birth and thus may have instructive roles during development. To test this hypothesis, we screened EC-secreted proteins for their ability to alter cell differentiation in alveolar organoids. We identified secreted protein acidic and rich in cysteine-like protein 1 (SPARCL1) as an extracellular matrix molecule that can promote alveolar type 2 (AT2) cell differentiation in vitro. SPARCL1-treated organoids display lysozyme upregulation and a doubling in the number of AT2 cells at the expense of intermediate progenitors. SPARCL1 also induces the upregulation of nuclear factor κB (NF-κB) target genes, and suppression of NF-κB activation in lung organoids blocked SPARCL1 effects. NF-κB activation by lipopolysaccharide (LPS) was sufficient to induce AT2 cell differentiation; however, pharmacological inhibition of the pathway alone did not prevent it. These data support a role for SPARCL1 and NF-κB in alveolar cell differentiation and suggest a potential value in targeting this signaling axis to promote alveolar maturation and regeneration.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102451"},"PeriodicalIF":5.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674519","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

Differentiation success of reprogrammed cells is heterogeneous in vivo and modulated by somatic cell identity memory. 重编程细胞的分化成功在体内是异质性的，并受体细胞身份记忆的调节。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-04-08 Epub Date: 2025-03-13 DOI: 10.1016/j.stemcr.2025.102447

Tomas Zikmund, Jonathan Fiorentino, Chris Penfold, Marco Stock, Polina Shpudeiko, Gaurav Agarwal, Larissa Langfeld, Kseniya Petrova, Leonid Peshkin, Stephan Hamperl, Antonio Scialdone, Eva Hoermanseder

{"title":"Differentiation success of reprogrammed cells is heterogeneous in vivo and modulated by somatic cell identity memory.","authors":"Tomas Zikmund, Jonathan Fiorentino, Chris Penfold, Marco Stock, Polina Shpudeiko, Gaurav Agarwal, Larissa Langfeld, Kseniya Petrova, Leonid Peshkin, Stephan Hamperl, Antonio Scialdone, Eva Hoermanseder","doi":"10.1016/j.stemcr.2025.102447","DOIUrl":"10.1016/j.stemcr.2025.102447","url":null,"abstract":"Nuclear reprogramming can change cellular fates. Yet, reprogramming efficiency is low, and the resulting cell types are often not functional. Here, we used nuclear transfer to eggs to follow single cells during reprogramming in vivo. We show that the differentiation success of reprogrammed cells varies across cell types and depends on the expression of genes specific to the previous cellular identity. We find subsets of reprogramming-resistant cells that fail to form functional cell types, undergo cell death, or disrupt normal body patterning. Reducing expression levels of genes specific to the cell type of origin leads to better reprogramming and improved differentiation trajectories. Thus, our work demonstrates that failing to reprogram in vivo is cell type specific and emphasizes the necessity of minimizing aberrant transcripts of the previous somatic identity for improving reprogramming.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102447"},"PeriodicalIF":5.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630959","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

Genetic variation modulates susceptibility to aberrant DNA hypomethylation and imprint deregulation in naive pluripotent stem cells. 遗传变异调节了幼稚多能干细胞对异常DNA低甲基化和印记去监管化的易感性。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-04-08 Epub Date: 2025-03-13 DOI: 10.1016/j.stemcr.2025.102450

C Parikh, R A Glenn, Y Shi, K Chatterjee, K Kasliwal, E E Swanzey, S Singer, S C Do, Y Zhan, Y Furuta, M Tahiliani, E Apostolou, A Polyzos, R Koche, J G Mezey, T Vierbuchen, M Stadtfeld

{"title":"Genetic variation modulates susceptibility to aberrant DNA hypomethylation and imprint deregulation in naive pluripotent stem cells.","authors":"C Parikh, R A Glenn, Y Shi, K Chatterjee, K Kasliwal, E E Swanzey, S Singer, S C Do, Y Zhan, Y Furuta, M Tahiliani, E Apostolou, A Polyzos, R Koche, J G Mezey, T Vierbuchen, M Stadtfeld","doi":"10.1016/j.stemcr.2025.102450","DOIUrl":"10.1016/j.stemcr.2025.102450","url":null,"abstract":"Naive pluripotent stem cells (nPSCs) frequently undergo pathological loss of DNA methylation at imprinted gene loci, posing a hurdle for biomedical applications and underscoring the need to identify underlying causes. We show that nPSCs from inbred mouse strains exhibit strain-specific susceptibility to locus-specific deregulation of imprinting marks during reprogramming and upon exposure to a mitogen-activated protein kinase (MAPK) inhibitor, a common approach to maintain naive pluripotency. Analysis of genetically diverse nPSCs from the Diversity Outbred (DO) stock confirms the impact of genetic variation on epigenome stability, which we leverage to identify trans-acting quantitative trait loci (QTLs) that modulate DNA methylation levels at specific targets or genome-wide. Analysis of multi-target QTLs on chromosomes 4 and 17 suggests candidate transcriptional regulators contributing to DNA methylation maintenance in nPSCs. We propose that genetic variants represent biomarkers to identify pluripotent cell lines with desirable properties and may allow the targeted engineering of nPSCs with stable epigenomes.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102450"},"PeriodicalIF":5.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630565","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

FOXO4-SP6 axis controls surface epithelium commitment by mediating epigenomic remodeling. FOXO4-SP6轴通过介导表观基因组重塑来控制表面上皮的承诺。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-04-08 Epub Date: 2025-03-13 DOI: 10.1016/j.stemcr.2025.102445

Jiafeng Liu, Huaxing Huang, Fengjiao An, Siqi Wu, Huizhen Guo, Bofeng Wang, Zhuo Han, Jieying Tan, Zesong Lin, Yihang Fang, Jinpeng Liu, Hanning Ye, Yuru Du, Kunlun Mo, Ying Huang, Mingsen Li, Li Wang, Zhen Mao, Hong Ouyang

{"title":"FOXO4-SP6 axis controls surface epithelium commitment by mediating epigenomic remodeling.","authors":"Jiafeng Liu, Huaxing Huang, Fengjiao An, Siqi Wu, Huizhen Guo, Bofeng Wang, Zhuo Han, Jieying Tan, Zesong Lin, Yihang Fang, Jinpeng Liu, Hanning Ye, Yuru Du, Kunlun Mo, Ying Huang, Mingsen Li, Li Wang, Zhen Mao, Hong Ouyang","doi":"10.1016/j.stemcr.2025.102445","DOIUrl":"10.1016/j.stemcr.2025.102445","url":null,"abstract":"Proper development of surface epithelium (SE) is a requisite for the normal development and function of ectodermal appendages; however, the molecular mechanisms underlying SE commitment remain largely unexplored. Here, we developed a KRT8 reporter system and utilized it to identify FOXO4 and SP6 as novel, essential regulators governing SE commitment. We found that the FOXO4-SP6 axis governs SE fate and its abrogation markedly impedes SE fate determination. Mechanistically, FOXO4 regulates SE initiation by shaping the SE chromatin accessibility landscape and regulating the deposition of H3K4me3. SP6, as a novel effector of FOXO4, activates SE-specific genes through modulating the H3K27ac deposition across their super-enhancers. Our work highlights the regulatory function of the FOXO4-SP6 axis in SE development, contributing to an improved understanding of SE fate decisions and providing a research foundation for the therapeutic application of ectodermal dysplasia.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102445"},"PeriodicalIF":5.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630362","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

Salt-inducible kinases transduce mechanical forces into the specification of the pancreatic endocrine lineage. 盐诱导激酶将机械力转化为胰腺内分泌谱系的规范。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-04-08 Epub Date: 2025-03-06 DOI: 10.1016/j.stemcr.2025.102444

Chenglei Tian, Adam Rump, Christine Ebeid, Anant Mamidi, Henrik Semb

{"title":"Salt-inducible kinases transduce mechanical forces into the specification of the pancreatic endocrine lineage.","authors":"Chenglei Tian, Adam Rump, Christine Ebeid, Anant Mamidi, Henrik Semb","doi":"10.1016/j.stemcr.2025.102444","DOIUrl":"10.1016/j.stemcr.2025.102444","url":null,"abstract":"The extracellular matrix-F-actin-Yes-associated protein 1 (YAP1)-Notch mechanosignaling axis is a gatekeeper in the fate decisions of bipotent pancreatic progenitors (bi-PPs). However, the link between F-actin dynamics and YAP1 activity remains poorly understood. Here, we identify salt-inducible kinases (SIKs) as mediators of F-actin-triggered changes in YAP1 activity. Interestingly, sodium chloride treatment promotes the differentiation of bi-PPs into NEUROG3+ endocrine progenitors (EPs) through enhanced SIK expression. Consistently, the pan-SIK inhibitor HG-9-09-01 (HG) inhibits latrunculin B (LatB)-induced EP differentiation via nuclear YAP1 accumulation. Unexpectedly, withdrawal of HG after a 12-h treatment increased SIK expression by a negative feedback mechanism, leading to significantly enhanced endocrinogenesis. Therefore, the combined treatment of bi-PPs with LatB and HG for 12 h boosted endocrinogenesis, ultimately leading to an increased number of beta cells. In summary, we identify SIKs as new transducers of mechanotransduction-triggered induction of pancreatic endocrine cell fates.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102444"},"PeriodicalIF":5.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586969","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

Robust generation of photoreceptor-dominant retinal organoids from porcine induced pluripotent stem cells. 从猪诱导的多能干细胞稳健地生成光感受器显性视网膜类器官。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-04-08 Epub Date: 2025-03-06 DOI: 10.1016/j.stemcr.2025.102425

Kimberly L Edwards, Bethany M Moore, Tyler-Serie Ganser, Praveen Joseph Susaimanickam, Kai Sovell, Yolana Martin, Lindsey D Jager, Ashley M Willes, Tyra H Moyer, Lydia Bowar, M Joseph Phillips, Ron Stewart, Li-Fang Chu, David M Gamm

{"title":"Robust generation of photoreceptor-dominant retinal organoids from porcine induced pluripotent stem cells.","authors":"Kimberly L Edwards, Bethany M Moore, Tyler-Serie Ganser, Praveen Joseph Susaimanickam, Kai Sovell, Yolana Martin, Lindsey D Jager, Ashley M Willes, Tyra H Moyer, Lydia Bowar, M Joseph Phillips, Ron Stewart, Li-Fang Chu, David M Gamm","doi":"10.1016/j.stemcr.2025.102425","DOIUrl":"10.1016/j.stemcr.2025.102425","url":null,"abstract":"Outer retinal degenerative diseases (RDDs) and injuries leading to photoreceptor (PR) loss are prevailing causes of blindness worldwide. While significant progress has been made in the manufacture of human pluripotent stem cell (hPSC)-derived PRs, robust production of pluripotent stem cell (PSC)-PRs from swine, a popular preclinical large animal model, would provide an avenue to collect conspecific functional and safety data to complement human xenograft studies. Toward this goal, we describe the highly efficient generation of PR-dominant porcine induced PSC (piPSC)-derived retinal organoids (ROs) using modifications of our established hPSC-RO differentiation protocol. Porcine iPSC-ROs were characterized using immunocytochemistry (ICC) and single-cell RNA sequencing (scRNA-seq), which revealed the presence and maturation of major neural retina cell types, including PRs and retinal ganglion cells, which possess molecular signatures akin to those found in hPSC-ROs. In late piPSC-ROs, a highly organized outer neuroepithelium was observed with rods and cones possessing outer segments and axon terminals expressing pre-synaptic markers adjacent to dendritic terminals of bipolar cells. The existence of piPSC lines and protocols that support reproducible, scalable production of female and male ROs will facilitate transplant studies in porcine models of retinal injury and RDDs unconfounded by immunological and evolutionary incompatibilities inherent to human xenografts.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102425"},"PeriodicalIF":5.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586878","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

Embracing the heterogeneity of neural stem cells in the subventricular zone. 拥抱室管膜下区神经干细胞的异质性。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-03-12 DOI: 10.1016/j.stemcr.2025.102452

Stefania Apostolou, Vanessa Donega

引用次数: 0

Safe CNV removal is crucial for successful hESC-RPE transplantation in wet age-related macular degeneration. 安全的CNV去除是湿性年龄相关性黄斑变性患者hESC-RPE移植成功的关键。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-03-11 Epub Date: 2025-02-27 DOI: 10.1016/j.stemcr.2025.102424

Ying Xue Lv, Qi You Li, Ping Duan, Min Fang Zhang, Bo Liu, Shi Ying Li, Tong Tao Zhao, Hao Wang, Yong Liu, Zheng Qin Yin

{"title":"Safe CNV removal is crucial for successful hESC-RPE transplantation in wet age-related macular degeneration.","authors":"Ying Xue Lv, Qi You Li, Ping Duan, Min Fang Zhang, Bo Liu, Shi Ying Li, Tong Tao Zhao, Hao Wang, Yong Liu, Zheng Qin Yin","doi":"10.1016/j.stemcr.2025.102424","DOIUrl":"10.1016/j.stemcr.2025.102424","url":null,"abstract":"Subretinal transplantation of human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells has demonstrated therapeutic potential in macular degeneration. However, its efficiency is limited in wet age-related macular degeneration (wet AMD) due to choroidal neovascularization (CNV). To investigate the feasibility of hESC-RPE cell transplantation, we employed a surgical approach to induce retinal detachment, which allowed the removal of CNV lesions. After retinal reattachment, hESC-RPE cells were transplanted into the subretinal space. Ten patients were enrolled and divided into 2 groups. No retinal edema or CNV recurrence was observed in group 1 (7 patients without bleeding). Group 2 (3 patients with bleeding) had persistent fundus inflammation, and one patient experienced CNV recurrence. All patients were managed effectively without vision loss. These findings suggest that subretinal transplantation of hESC-RPE cells after CNV removal is safe and well tolerated; however, damage caused during CNV removal may trigger persistent inflammation and CNV recurrence. This study was registered at ClinicalTrials.gov (NCT02749734).","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102424"},"PeriodicalIF":5.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531796","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

Response to Yu et al. 对Yu等人的回应。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-03-11 Epub Date: 2025-02-06 DOI: 10.1016/j.stemcr.2025.102400

Yuanyue Liu, Siqi Song, Youyu Liu, Ting Fu, Yanzheng Guo, Ruoqing Liu, Jiexing Chen, Yanchun Lin, Yaqi Cheng, Yun Li, Tian Guan, Shiqi Ling, Haoyu Zeng

引用次数: 0

20 years of stemness: From stem cells to hypertranscription and back. 20年的干细胞：从干细胞到超转录再回来。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-03-11 Epub Date: 2025-02-06 DOI: 10.1016/j.stemcr.2025.102406

Yun-Kyo Kim, Miguel Ramalho-Santos

引用次数: 0