Stem Cell Reports最新文献_第3页

Neural crest precursors from the skin are the primary source of directly reprogrammed neurons. 来自皮肤的神经嵴前体是直接重编程神经元的主要来源。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-11-12 Epub Date: 2024-10-31 DOI: 10.1016/j.stemcr.2024.10.003

Justin J Belair-Hickey, Ahmed Fahmy, Wenbo Zhang, Rifat S Sajid, Brenda L K Coles, Michael W Salter, Derek van der Kooy

{"title":"Neural crest precursors from the skin are the primary source of directly reprogrammed neurons.","authors":"Justin J Belair-Hickey, Ahmed Fahmy, Wenbo Zhang, Rifat S Sajid, Brenda L K Coles, Michael W Salter, Derek van der Kooy","doi":"10.1016/j.stemcr.2024.10.003","DOIUrl":"10.1016/j.stemcr.2024.10.003","url":null,"abstract":"Direct reprogramming involves the conversion of differentiated cell types without returning to an earlier developmental state. Here, we explore how heterogeneity in developmental lineage and maturity of the starting cell population contributes to direct reprogramming using the conversion of murine fibroblasts into neurons. Our hypothesis is that a single lineage of cells contributes to most reprogramming and that a rare elite precursor with intrinsic bias is the source of reprogrammed neurons. We find that nearly all reprogrammed neurons are derived from the neural crest (NC) lineage. Moreover, when rare proliferating NC precursors are selectively ablated, there is a large reduction in the number of reprogrammed neurons. Previous interpretations of this paradigm are that it demonstrates a cell fate conversion across embryonic germ layers (mesoderm to ectoderm). Our interpretation is that this is actually directed differentiation of a neural lineage stem cell in the skin that has intrinsic bias to produce neuronal progeny.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1620-1634"},"PeriodicalIF":5.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565073","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

Lineage-specific dynamics of loss of X upregulation during inactive-X reactivation. 无活性-X 再激活过程中 X 缺失上调的特定系动态。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-11-12 Epub Date: 2024-10-31 DOI: 10.1016/j.stemcr.2024.10.001

Hemant Chandru Naik, Deepshikha Chandel, Sudeshna Majumdar, Maniteja Arava, Runumi Baro, Harshavardhan Bv, Kishore Hari, Parichitran Ayyamperumal, Avinchal Manhas, Mohit Kumar Jolly, Srimonta Gayen

{"title":"Lineage-specific dynamics of loss of X upregulation during inactive-X reactivation.","authors":"Hemant Chandru Naik, Deepshikha Chandel, Sudeshna Majumdar, Maniteja Arava, Runumi Baro, Harshavardhan Bv, Kishore Hari, Parichitran Ayyamperumal, Avinchal Manhas, Mohit Kumar Jolly, Srimonta Gayen","doi":"10.1016/j.stemcr.2024.10.001","DOIUrl":"10.1016/j.stemcr.2024.10.001","url":null,"abstract":"In mammals, X chromosome dosage is balanced between sexes through the silencing of one X chromosome in females. Recent single-cell RNA sequencing analysis demonstrated that the inactivation of the X chromosome is accompanied by the upregulation of the active X chromosome (Xa) during mouse embryogenesis. Here, we have investigated if the reactivation of inactive-X (Xi) leads to the loss of Xa upregulation in different cellular or developmental contexts. We find that while Xi reactivation and loss of Xa upregulation are tightly coupled in mouse embryonic epiblast and induced pluripotent stem cells, that is not the case in germ cells. Moreover, we demonstrate that partial reactivation of Xi in mouse extra-embryonic endoderm stem cells and human B cells does not result in the loss of Xa upregulation. Finally, we have established a mathematical model for the transcriptional coordination of two X chromosomes. Together, we conclude that the reactivation of Xi is not always synchronized with the loss of Xa upregulation.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1564-1582"},"PeriodicalIF":5.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565072","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

Abnormal synaptic architecture in iPSC-derived neurons from a multi-generational family with genetic Creutzfeldt-Jakob disease. 遗传性克雅氏病多代家族 iPSC 衍生神经元的异常突触结构。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-10-08 Epub Date: 2024-09-26 DOI: 10.1016/j.stemcr.2024.08.010

Aldana D Gojanovich, Nhat T T Le, Robert C C Mercer, Seonmi Park, Bei Wu, Alice Anane, Janelle S Vultaggio, Gustavo Mostoslavsky, David A Harris

{"title":"Abnormal synaptic architecture in iPSC-derived neurons from a multi-generational family with genetic Creutzfeldt-Jakob disease.","authors":"Aldana D Gojanovich, Nhat T T Le, Robert C C Mercer, Seonmi Park, Bei Wu, Alice Anane, Janelle S Vultaggio, Gustavo Mostoslavsky, David A Harris","doi":"10.1016/j.stemcr.2024.08.010","DOIUrl":"10.1016/j.stemcr.2024.08.010","url":null,"abstract":"Genetic prion diseases are caused by mutations in PRNP, which encodes the prion protein (PrPC). Why these mutations are pathogenic, and how they alter the properties of PrPC are poorly understood. We have consented and accessed 22 individuals of a multi-generational Israeli family harboring the highly penetrant E200K PRNP mutation and generated a library of induced pluripotent stem cells (iPSCs) representing nine carriers and four non-carriers. iPSC-derived neurons from E200K carriers display abnormal synaptic architecture characterized by misalignment of postsynaptic NMDA receptors with the cytoplasmic scaffolding protein PSD95. Differentiated neurons from mutation carriers do not produce PrPSc, the aggregated and infectious conformer of PrP, suggesting that loss of a physiological function of PrPC may contribute to the disease phenotype. Our study shows that iPSC-derived neurons can provide important mechanistic insights into the pathogenesis of genetic prion diseases and can offer a powerful platform for testing candidate therapeutics.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1474-1488"},"PeriodicalIF":5.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354092","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

SMAD3 mediates the specification of human induced pluripotent stem cell-derived epicardium into progenitors for the cardiac pericyte lineage. SMAD3介导人类诱导多能干细胞衍生的心外膜向心脏周细胞系祖细胞的分化。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-10-08 Epub Date: 2024-09-26 DOI: 10.1016/j.stemcr.2024.08.008

Yutaro Miyoshi, Antonio Lucena-Cacace, Yu Tian, Yasuko Matsumura, Kanae Tani, Misato Nishikawa, Megumi Narita, Takeshi Kimura, Koh Ono, Yoshinori Yoshida

{"title":"SMAD3 mediates the specification of human induced pluripotent stem cell-derived epicardium into progenitors for the cardiac pericyte lineage.","authors":"Yutaro Miyoshi, Antonio Lucena-Cacace, Yu Tian, Yasuko Matsumura, Kanae Tani, Misato Nishikawa, Megumi Narita, Takeshi Kimura, Koh Ono, Yoshinori Yoshida","doi":"10.1016/j.stemcr.2024.08.008","DOIUrl":"10.1016/j.stemcr.2024.08.008","url":null,"abstract":"Understanding the molecular mechanisms of epicardial epithelial-to-mesenchymal transition (EMT), particularly in directing cell fate toward epicardial derivatives, is crucial for regenerative medicine using human induced pluripotent stem cell (iPSC)-derived epicardium. Although transforming growth factor β (TGF-β) plays a pivotal role in epicardial biology, orchestrating EMT during embryonic development via downstream signaling through SMAD proteins, the function of SMAD proteins in the epicardium in maintaining vascular homeostasis or mediating the differentiation of various epicardial-derived cells (EPDCs) is not yet well understood. Our study reveals that TGF-β-independent SMAD3 expression autonomously predicts epicardial cell specification and lineage maintenance, acting as a key mediator in promoting the angiogenic-oriented specification of the epicardium into cardiac pericyte progenitors. This finding uncovers a novel role for SMAD3 in the human epicardium, particularly in generating cardiac pericyte progenitors that enhance cardiac microvasculature angiogenesis. This insight opens new avenues for leveraging epicardial biology in developing more effective cardiac regeneration strategies.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1399-1416"},"PeriodicalIF":5.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354106","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

Scaled and efficient derivation of loss-of-function alleles in risk genes for neurodevelopmental and psychiatric disorders in human iPSCs. 在人类 iPSCs 中大规模、高效地衍生神经发育和精神疾病风险基因的功能缺失等位基因。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-10-08 Epub Date: 2024-09-12 DOI: 10.1016/j.stemcr.2024.08.003

Hanwen Zhang, Ada McCarroll, Lilia Peyton, Sol Díaz de León-Guerrerro, Siwei Zhang, Prarthana Gowda, David Sirkin, Mahmoud ElAchwah, Alexandra Duhe, Whitney G Wood, Brandon Jamison, Gregory Tracy, Rebecca Pollak, Ronald P Hart, Carlos N Pato, Jennifer G Mulle, Alan R Sanders, Zhiping P Pang, Jubao Duan

{"title":"Scaled and efficient derivation of loss-of-function alleles in risk genes for neurodevelopmental and psychiatric disorders in human iPSCs.","authors":"Hanwen Zhang, Ada McCarroll, Lilia Peyton, Sol Díaz de León-Guerrerro, Siwei Zhang, Prarthana Gowda, David Sirkin, Mahmoud ElAchwah, Alexandra Duhe, Whitney G Wood, Brandon Jamison, Gregory Tracy, Rebecca Pollak, Ronald P Hart, Carlos N Pato, Jennifer G Mulle, Alan R Sanders, Zhiping P Pang, Jubao Duan","doi":"10.1016/j.stemcr.2024.08.003","DOIUrl":"10.1016/j.stemcr.2024.08.003","url":null,"abstract":"Translating genetic findings for neurodevelopmental and psychiatric disorders (NPDs) into actionable disease biology would benefit from large-scale and unbiased functional studies of NPD genes. Leveraging the cytosine base editing (CBE) system, we developed a pipeline for clonal loss-of-function (LoF) allele mutagenesis in human induced pluripotent stem cells (hiPSCs) by introducing premature stop codons (iSTOP) that lead to mRNA nonsense-mediated decay (NMD) or protein truncation. We tested the pipeline for 23 NPD genes on 3 hiPSC lines and achieved highly reproducible, efficient iSTOP editing in 22 genes. Using RNA sequencing (RNA-seq), we confirmed their pluripotency, absence of chromosomal abnormalities, and NMD. Despite high editing efficiency, three schizophrenia risk genes (SETD1A, TRIO, and CUL1) only had heterozygous LoF alleles, suggesting their essential roles for cell growth. We found that CUL1-LoF reduced neurite branches and synaptic puncta density. This iSTOP pipeline enables a scaled and efficient LoF mutagenesis of NPD genes, yielding an invaluable shareable resource.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1489-1504"},"PeriodicalIF":5.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142295962","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

Astrocytes originated from neural stem cells drive the regenerative remodeling of pathologic CSPGs in spinal cord injury. 源自神经干细胞的星形胶质细胞推动了脊髓损伤中病理性 CSPG 的再生重塑。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-10-08 Epub Date: 2024-09-19 DOI: 10.1016/j.stemcr.2024.08.007

Seyed Mojtaba Hosseini, Shiva Nemati, Soheila Karimi-Abdolrezaee

{"title":"Astrocytes originated from neural stem cells drive the regenerative remodeling of pathologic CSPGs in spinal cord injury.","authors":"Seyed Mojtaba Hosseini, Shiva Nemati, Soheila Karimi-Abdolrezaee","doi":"10.1016/j.stemcr.2024.08.007","DOIUrl":"10.1016/j.stemcr.2024.08.007","url":null,"abstract":"Neural degeneration is a hallmark of spinal cord injury (SCI). Multipotent neural precursor cells (NPCs) have the potential to reconstruct the damaged neuron-glia network due to their tri-lineage capacity to generate neurons, astrocytes, and oligodendrocytes. However, astrogenesis is the predominant fate of resident or transplanted NPCs in the SCI milieu adding to the abundant number of resident astrocytes in the lesion. How NPC-derived astrocytes respond to the inflammatory milieu of SCI and the mechanisms by which they contribute to the post-injury recovery processes remain largely unknown. Here, we uncover that activated NPC-derived astrocytes exhibit distinct molecular signature that is immune modulatory and foster neurogenesis, neuronal maturity, and synaptogenesis. Mechanistically, NPC-derived astrocytes perform regenerative matrix remodeling by clearing inhibitory chondroitin sulfate proteoglycans (CSPGs) from the injury milieu through LAR and PTP-σ receptor-mediated endocytosis and the production of ADAMTS1 and ADAMTS9, while most resident astrocytes are pro-inflammatory and contribute to the pathologic deposition of CSPGs. These novel findings unravel critical mechanisms of NPC-mediated astrogenesis in SCI repair.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1451-1473"},"PeriodicalIF":5.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142295959","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

Guidelines for managing and using the digital phenotypes of pluripotent stem cell lines. 多能干细胞系数字表型的管理和使用指南。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-10-08 Epub Date: 2024-09-26 DOI: 10.1016/j.stemcr.2024.08.009

Christine A Wells, Anke Guhr, Amos Bairoch, Ying Chen, Mengqi Hu, Peter Löser, Tenneille E Ludwig, Nancy Mah, Sabine C Mueller, Andrea E M Seiler Wulczyn, Stefanie Seltmann, Bella Rossbach, Andreas Kurtz

引用次数: 0

Functionally redundant roles of ID family proteins in spermatogonial stem cells. ID家族蛋白在精原干细胞中的功能冗余作用

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-10-08 Epub Date: 2024-09-26 DOI: 10.1016/j.stemcr.2024.08.011

Hue M La, Ai-Leen Chan, Ashlee M Hutchinson, Bianka Y M Su, Fernando J Rossello, Ralf B Schittenhelm, Robin M Hobbs

{"title":"Functionally redundant roles of ID family proteins in spermatogonial stem cells.","authors":"Hue M La, Ai-Leen Chan, Ashlee M Hutchinson, Bianka Y M Su, Fernando J Rossello, Ralf B Schittenhelm, Robin M Hobbs","doi":"10.1016/j.stemcr.2024.08.011","DOIUrl":"10.1016/j.stemcr.2024.08.011","url":null,"abstract":"Spermatogonial stem cells (SSCs) are essential for sustained sperm production, but SSC regulatory mechanisms and markers remain poorly defined. Studies have suggested that the Id family transcriptional regulator Id4 is expressed in SSCs and involved in SSC maintenance. Here, we used reporter and knockout models to define the expression and function of Id4 in the adult male germline. Within the spermatogonial pool, Id4 reporter expression and inhibitor of DNA-binding 4 (ID4) protein are found throughout the GFRα1+ fraction, comprising the self-renewing population. However, Id4 deletion is tolerated by adult SSCs while revealing roles in meiotic spermatocytes. Cultures of undifferentiated spermatogonia could be established following Id4 deletion. Importantly, ID4 loss in undifferentiated spermatogonia triggers ID3 upregulation, and both ID proteins associate with transcription factor partner TCF3 in wild-type cells. Combined inhibition of IDs in cultured spermatogonia disrupts the stem cell state and blocks proliferation. Our data therefore demonstrate critical but functionally redundant roles of IDs in SSC function.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1379-1388"},"PeriodicalIF":5.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354104","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

EZH2 Protects Glioma Stem Cells from Radiation-Induced Cell Death in a MELK/FOXM1-Dependent Manner. EZH2 以 MELK/FOXM1 依赖性方式保护胶质瘤干细胞免受辐射诱导的细胞死亡。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-10-08 Epub Date: 2024-09-15 DOI: 10.1016/j.stemcr.2024.09.003

Sung-Hak Kim, Kaushal Joshi, Ravesanker Ezhilarasan, Toshia R Myers, Jason Siu, Chunyu Gu, Mariko Nakano-Okuno, David Taylor, Mutsuko Minata, Erik P Sulman, Jeongwu Lee, Krishna P L Bhat, Anna Elisabetta Salcini, Ichiro Nakano

引用次数: 0

Rod-shaped micropatterning enhances the electrophysiological maturation of cardiomyocytes derived from human induced pluripotent stem cells. 棒状微图案化可增强人类诱导多能干细胞心肌细胞的电生理成熟。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-10-08 Epub Date: 2024-09-19 DOI: 10.1016/j.stemcr.2024.08.005

Zeina R Al Sayed, Charlène Jouve, Magali Seguret, Andrea Ruiz-Velasco, Céline Pereira, David-Alexandre Trégouët, Jean-Sébastien Hulot

{"title":"Rod-shaped micropatterning enhances the electrophysiological maturation of cardiomyocytes derived from human induced pluripotent stem cells.","authors":"Zeina R Al Sayed, Charlène Jouve, Magali Seguret, Andrea Ruiz-Velasco, Céline Pereira, David-Alexandre Trégouët, Jean-Sébastien Hulot","doi":"10.1016/j.stemcr.2024.08.005","DOIUrl":"10.1016/j.stemcr.2024.08.005","url":null,"abstract":"Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offer great potential for drug screening and disease modeling. However, hiPSC-CMs remain immature compared to the adult cardiac cells. Cardiomyocytes isolated from adult human hearts have a typical rod-shaped morphology. Here, we sought to develop a simple method to improve the architectural maturity of hiPSC-CMs by using a rod-shaped cell micropatterned substrate consisting of repeated rectangles (120 μm long × 30 μm wide) surrounded by a chemical cell repellent. The generated hiPSC-CMs exhibit numerous characteristics similar to adult human cardiomyocytes, including elongated cell shape, well-organized sarcomeres, and increased myofibril density. The improvement in structural properties correlates with the enrichment of late ventricular action potentials characterized by a more hyperpolarized resting membrane potential and an enhanced depolarization consistent with an increased sodium current density. The more mature hiPSC-CMs generated by this method may serve as a useful in vitro platform for characterizing cardiovascular disease.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1417-1431"},"PeriodicalIF":5.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142295961","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