Stem Cell Reports最新文献_第2页

Spatial transcriptomics reveals molecular cues underlying the site specificity of the adult mouse oral mucosa and its stem cell niches. 空间转录组学揭示了成年小鼠口腔黏膜及其干细胞龛位部位特异性的分子线索。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-11-11 DOI: 10.1016/j.stemcr.2024.10.007

Anna C Seubert, Marion Krafft, Sarah Bopp, Moutaz Helal, Pranjali Bhandare, Elmar Wolf, Anna Alemany, Angela Riedel, Kai Kretzschmar

{"title":"Spatial transcriptomics reveals molecular cues underlying the site specificity of the adult mouse oral mucosa and its stem cell niches.","authors":"Anna C Seubert, Marion Krafft, Sarah Bopp, Moutaz Helal, Pranjali Bhandare, Elmar Wolf, Anna Alemany, Angela Riedel, Kai Kretzschmar","doi":"10.1016/j.stemcr.2024.10.007","DOIUrl":"https://doi.org/10.1016/j.stemcr.2024.10.007","url":null,"abstract":"The oral cavity is a multifunctional organ composed of structurally heterogeneous mucosal tissues that remain poorly characterized. Oral mucosal tissues are highly stratified and segmented along an epithelial-lamina propria axis. Here, we performed spatial transcriptomics (tomo-seq) on the tongue, cheeks, and palate of the adult mouse to understand the cues that maintain the oral mucosal sites. We define molecular markers of unique and shared cellular niches and differentiation programs across oral sites. Using a comparative approach, we identify fibroblast growth factor (FGF) pathway components as potential stem cell niche factors for oral epithelial stem cells. Using organoid-forming efficiency assays, we validated three FGF ligands (FGF1, FGF7, and FGF10) as site-specific niche factors in the dorsal and ventral tongue. Our dataset of the spatially resolved genes across major oral sites represents a comprehensive resource for unraveling the molecular mechanisms underlying the adult homeostasis of the oral mucosa and its stem cell niches.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Amendments to ASRM: Can we move away from a "Therapeutic Haven"? ASRM 修正案：我们能否放弃 "治疗天堂"？

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-11-05 DOI: 10.1016/j.stemcr.2024.10.006

Tsunakuni Ikka, Taichi Hatta, Misao Fujita

引用次数: 0

Bone morphogenetic protein 4 induces hematopoietic stem cell development from murine hemogenic endothelial cells in culture. 骨形态发生蛋白 4 可诱导小鼠造血内皮细胞的造血干细胞发育。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-11-03 DOI: 10.1016/j.stemcr.2024.10.005

Mariko Tsuruda, Saori Morino-Koga, Xueyu Zhao, Shingo Usuki, Kei-Ichiro Yasunaga, Tomomasa Yokomizo, Ryuichi Nishinakamura, Toshio Suda, Minetaro Ogawa

{"title":"Bone morphogenetic protein 4 induces hematopoietic stem cell development from murine hemogenic endothelial cells in culture.","authors":"Mariko Tsuruda, Saori Morino-Koga, Xueyu Zhao, Shingo Usuki, Kei-Ichiro Yasunaga, Tomomasa Yokomizo, Ryuichi Nishinakamura, Toshio Suda, Minetaro Ogawa","doi":"10.1016/j.stemcr.2024.10.005","DOIUrl":"https://doi.org/10.1016/j.stemcr.2024.10.005","url":null,"abstract":"Hematopoietic stem cells (HSCs) develop from hemogenic endothelial cells (HECs) during mouse embryogenesis. Understanding the signaling molecules required for HSC development is crucial for the in vitro derivation of HSCs. We previously induced HSCs from embryonic HECs, isolated at embryonic day 10.5 (E10.5), in serum-free culture conditions with stem cell factor, thrombopoietin, and an endothelial feeder layer. Here, we aimed to elucidate signal requirements for inducing HSCs from earlier-stage HECs. Single-cell RNA sequencing (RNA-seq) analysis detected bone morphogenetic protein (BMP) signaling activation in E9.5 HECs. Adding BMP4 to the culture conditions led to the induction of HSCs from E9.5 HECs. Furthermore, isolating BMP4 receptor-expressing HECs from E9.5 embryos enriched progenitors with HSC-forming ability. This study identified BMP4 as an essential factor promoting the differentiation of early HECs into HSCs, opening up new possibilities for the in vitro derivation of HSCs.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Derivation of transplantable human thyroid follicular epithelial cells from induced pluripotent stem cells. 从诱导多能干细胞中衍生出可移植的人类甲状腺滤泡上皮细胞。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-10-25 DOI: 10.1016/j.stemcr.2024.10.004

Hendrik J Undeutsch, Alberto Posabella, Andrea B Alber, Pushpinder S Bawa, Carlos Villacorta-Martin, Feiya Wang, Laertis Ikonomou, Darrell N Kotton, Anthony N Hollenberg

{"title":"Derivation of transplantable human thyroid follicular epithelial cells from induced pluripotent stem cells.","authors":"Hendrik J Undeutsch, Alberto Posabella, Andrea B Alber, Pushpinder S Bawa, Carlos Villacorta-Martin, Feiya Wang, Laertis Ikonomou, Darrell N Kotton, Anthony N Hollenberg","doi":"10.1016/j.stemcr.2024.10.004","DOIUrl":"https://doi.org/10.1016/j.stemcr.2024.10.004","url":null,"abstract":"The production of mature functioning thyroid follicular cells (TFCs) from human induced pluripotent stem cells (iPSCs) is critical for potential novel therapeutic approaches to post-surgical and congenital hypothyroidism. To accomplish this, we developed a novel human iPSC line that expresses fluorophores targeted to the NKX2-1 and PAX8 loci, allowing for the identification and purification of cells destined to become TFCs. Optimizing a sequence of defined, serum-free media to promote stepwise developmental directed differentiation, we found that bone morphogenic protein 4 (BMP4) and fibroblast growth factor 2 (FGF2) stimulated lineage specification into TFCs from multiple iPSC lines. Single-cell RNA sequencing demonstrated that BMP4 withdrawal after lineage specification promoted TFC maturation, with mature TFCs representing the majority of cells present within 1 month. After xenotransplantation into athyreotic immunodeficient mice, engrafted cells exhibited thyroid follicular organization with thyroglobulin protein detected in the lumens of NKX2-1-positive follicles. While our iPSC-derived TFCs presented durable expression of thyroid-specific proteins, they were unable to rescue hypothyroidism in vivo.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","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