Stem Cell Reports最新文献

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 : 2024-10-24 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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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 : 2024-10-22 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

引用次数: 0

Genome-wide screening reveals essential roles for HOX genes and imprinted genes during caudal neurogenesis of human embryonic stem cells. 全基因组筛选揭示了 HOX 基因和印记基因在人类胚胎干细胞尾部神经发生过程中的重要作用。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-10-21 DOI: 10.1016/j.stemcr.2024.09.009

Shay Kinreich, Anna Bialer-Tsypin, Ruth Viner-Breuer, Gal Keshet, Roni Suhler, Patrick Siang Lin Lim, Tamar Golan-Lev, Ofra Yanuka, Adi Turjeman, Oren Ram, Eran Meshorer, Dieter Egli, Atilgan Yilmaz, Nissim Benvenisty

{"title":"Genome-wide screening reveals essential roles for HOX genes and imprinted genes during caudal neurogenesis of human embryonic stem cells.","authors":"Shay Kinreich, Anna Bialer-Tsypin, Ruth Viner-Breuer, Gal Keshet, Roni Suhler, Patrick Siang Lin Lim, Tamar Golan-Lev, Ofra Yanuka, Adi Turjeman, Oren Ram, Eran Meshorer, Dieter Egli, Atilgan Yilmaz, Nissim Benvenisty","doi":"10.1016/j.stemcr.2024.09.009","DOIUrl":"https://doi.org/10.1016/j.stemcr.2024.09.009","url":null,"abstract":"Mapping the essential pathways for neuronal differentiation can uncover new therapeutics and models for neurodevelopmental disorders. We thus utilized a genome-wide loss-of-function library in haploid human embryonic stem cells, differentiated into caudal neuronal cells. We show that essential genes for caudal neurogenesis are enriched for secreted and membrane proteins and that a large group of neurological conditions, including neurodegenerative disorders, manifest early neuronal phenotypes. Furthermore, essential transcription factors are enriched with homeobox (HOX) genes demonstrating synergistic regulation and surprising non-redundant functions between HOXA6 and HOXB6 paralogs. Moreover, we establish the essentialome of imprinted genes during neurogenesis, demonstrating that maternally expressed genes are non-essential in pluripotent cells and their differentiated germ layers, yet several are essential for neuronal development. These include Beckwith-Wiedemann syndrome- and Angelman syndrome-related genes, for which we suggest a novel regulatory pathway. Overall, our work identifies essential pathways for caudal neuronal differentiation and stage-specific phenotypes of neurological disorders.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565036","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

Guardians of the mind: Calvarial stem cells and brain border immunity. 心灵的守护者钙质干细胞与脑边界免疫力

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-10-19 DOI: 10.1016/j.stemcr.2024.10.002

Bo Li

引用次数: 0

The urgent need for clear and concise regulations on exosome-based interventions. 亟需对基于外泌体的干预措施制定简明扼要的规定。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-10-12 DOI: 10.1016/j.stemcr.2024.09.008

Misao Fujita, Taichi Hatta, Tsunakuni Ikka, Tatsuo Onishi

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":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting glioblastoma with a brain-penetrant drug that impairs brain tumor stem cells via NLE1-Notch1 complex. 通过 NLE1-Notch1 复合物损害脑肿瘤干细胞的脑穿刺药物靶向胶质母细胞瘤。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-10-08 DOI: 10.1016/j.stemcr.2024.09.007

Audrey Burban, Ahmad Sharanek, Aldo Hernandez-Corchado, Hamed S Najafabadi, Vahab D Soleimani, Arezu Jahani-Asl

{"title":"Targeting glioblastoma with a brain-penetrant drug that impairs brain tumor stem cells via NLE1-Notch1 complex.","authors":"Audrey Burban, Ahmad Sharanek, Aldo Hernandez-Corchado, Hamed S Najafabadi, Vahab D Soleimani, Arezu Jahani-Asl","doi":"10.1016/j.stemcr.2024.09.007","DOIUrl":"https://doi.org/10.1016/j.stemcr.2024.09.007","url":null,"abstract":"Brain tumor stem cells (BTSCs) are a population of self-renewing malignant stem cells that play an important role in glioblastoma tumor hierarchy and contribute to tumor growth, therapeutic resistance, and tumor relapse. Thus, targeting of BTSCs within the bulk of tumors represents a crucial therapeutic strategy. Here, we report that edaravone is a potent drug that impairs BTSCs in glioblastoma. We show that edaravone inhibits the self-renewal and growth of BTSCs harboring a diverse range of oncogenic mutations without affecting non-oncogenic neural stem cells. Global gene expression analysis revealed that edaravone significantly alters BTSC transcriptome and attenuates the expression of a large panel of genes involved in cell cycle progression, stemness, and DNA repair mechanisms. Mechanistically, we discovered that edaravone directly targets Notchless homolog 1 (NLE1) and impairs Notch signaling pathway, alters the expression of stem cell markers, and sensitizes BTSC response to ionizing radiation (IR)-induced cell death. Importantly, we show that edaravone treatment in preclinical models delays glioblastoma tumorigenesis, sensitizes their response to IR, and prolongs the lifespan of animals. Our data suggest that repurposing of edaravone is a promising therapeutic strategy for patients with glioblastoma.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475174","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

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":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0