Stem Cell Reports最新文献

Glycogen synthase kinase-3 inhibition and insulin enhance proliferation and inhibit maturation of human iPSC-derived cardiomyocytes via TCF and FOXO signaling. 糖原合成酶激酶-3抑制和胰岛素通过TCF和FOXO信号通路增强人ipsc源性心肌细胞的增殖和抑制成熟。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-01-14 Epub Date: 2024-12-05 DOI: 10.1016/j.stemcr.2024.11.001

Qianliang Yuan, Devin Verbueken, Rafeeh Dinani, Rosa Kim, Eric Schoger, Chloé D Morsink, Shamim Amiri Simkooei, Luuk J M Kemna, Jesper Hjortnaes, Diederik W D Kuster, Reinier A Boon, Laura Cecilia Zelarayan, Jolanda van der Velden, Jan W Buikema

{"title":"Glycogen synthase kinase-3 inhibition and insulin enhance proliferation and inhibit maturation of human iPSC-derived cardiomyocytes via TCF and FOXO signaling.","authors":"Qianliang Yuan, Devin Verbueken, Rafeeh Dinani, Rosa Kim, Eric Schoger, Chloé D Morsink, Shamim Amiri Simkooei, Luuk J M Kemna, Jesper Hjortnaes, Diederik W D Kuster, Reinier A Boon, Laura Cecilia Zelarayan, Jolanda van der Velden, Jan W Buikema","doi":"10.1016/j.stemcr.2024.11.001","DOIUrl":"10.1016/j.stemcr.2024.11.001","url":null,"abstract":"Embryonic signaling pathways exert stage-specific effects during cardiac development, yet the precise signals for proliferation or maturation remain elusive. To uncover the cues for proliferation, we performed a combinatory cell-cycle screen for insulin and glycogen synthase kinase-3 (GSK3) inhibition in spontaneously beating human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Our analysis for proliferation, and subsequential downstream sarcomere development, gene expression analysis, and molecular interventions identified a temporal interplay between insulin/Akt/FOXO and CHIR99021/Wnt/GSK3/TCF signaling. Combined pathway activation led to proliferation of immature hiPSC-CMs with low sarcomere and mitochondria content, while, in the absence of pathway activators, cardiomyocytes rapidly exited the cell cycle and fetched higher organization of sarcomeres and mitochondria. Our data demonstrate two important pathways, which enhance proliferation and inhibit maturation, and provide molecular mechanistic understanding of these cell fate decisions in immature hiPSC-CMs.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102371"},"PeriodicalIF":5.9,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792173","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

PKM2 is a key factor to regulate neurogenesis and cognition by controlling lactate homeostasis. PKM2是通过控制乳酸稳态调节神经发生和认知的关键因子。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-01-14 Epub Date: 2024-12-19 DOI: 10.1016/j.stemcr.2024.11.011

Pengyan He, Bingjun Zhang, Wei Jiang, Fan Zhu, Ziqi Liang, Lin Gao, Yuhong Zhang, Yuge Wang, Caixia Wu, Changyong Tang

{"title":"PKM2 is a key factor to regulate neurogenesis and cognition by controlling lactate homeostasis.","authors":"Pengyan He, Bingjun Zhang, Wei Jiang, Fan Zhu, Ziqi Liang, Lin Gao, Yuhong Zhang, Yuge Wang, Caixia Wu, Changyong Tang","doi":"10.1016/j.stemcr.2024.11.011","DOIUrl":"10.1016/j.stemcr.2024.11.011","url":null,"abstract":"Adult hippocampal neurogenesis (AHN), the process of generating new neurons from adult neural stem/progenitor cells (NSPCs), is crucial for cognitive functions and is influenced by numerous factors, including metabolic processes. Pyruvate kinase M2 (PKM2), a key rate-limiting enzyme in glycolysis, catalyzes the production of pyruvate, which undergoes either oxidative phosphorylation or anaerobic oxidation. We observed that PKM2 is highly expressed in NSPCs, but its significance remains unclear for AHN and cognition. Using knockdown or knockout strategies, we discovered that PKM2 deficiency led to reduced AHN and impaired cognitive functions. Furthermore, we observed that knockout of PKM2 resulted in lower L-lactate levels, and supplementing L-lactate in PKM2 knockout mice improved AHN and cognitive functions. Mechanistically, L-lactate restored neurogenesis via monocarboxylate transporter 2 (MCT2), but not hydroxycarboxylic acid receptor 1. In summary, our findings demonstrate that PKM2 is essential for AHN, and lactate supplementation can restore neurogenesis in an MCT2-dependent manner.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102381"},"PeriodicalIF":5.9,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872826","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

Heparan sulfate regulates the fate decisions of human pluripotent stem cells. 硫酸乙酰肝素调节人类多能干细胞的命运决定。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-01-14 Epub Date: 2024-12-26 DOI: 10.1016/j.stemcr.2024.11.014

Deepsing Syangtan, Deena Al Mahbuba, Sayaka Masuko, Qiao Li, Andrew C Elton, Yefim Zaltsman, Paul J Wrighton, Ke Xia, Xiaorui Han, Yilan Ouyang, Fuming Zhang, Robert J Linhardt, Laura L Kiessling

{"title":"Heparan sulfate regulates the fate decisions of human pluripotent stem cells.","authors":"Deepsing Syangtan, Deena Al Mahbuba, Sayaka Masuko, Qiao Li, Andrew C Elton, Yefim Zaltsman, Paul J Wrighton, Ke Xia, Xiaorui Han, Yilan Ouyang, Fuming Zhang, Robert J Linhardt, Laura L Kiessling","doi":"10.1016/j.stemcr.2024.11.014","DOIUrl":"10.1016/j.stemcr.2024.11.014","url":null,"abstract":"Heparan sulfate (HS) is an anionic polysaccharide generated by all animal cells, but our understanding of its roles in human pluripotent stem cell (hPSC) self-renewal and differentiation is limited. We derived HS-deficient hPSCs by disrupting the EXT1 glycosyltransferase. These EXT1-/- hPSCs maintain self-renewal and pluripotency under standard culture conditions that contain high levels of basic fibroblast growth factor(bFGF), a requirement for sufficient bFGF signaling in the engineered cells. Intriguingly, Activin/Nodal signaling is also compromised in EXT1-/- hPSCs, highlighting HS's previously unexplored involvement in this pathway. As a result, EXT1-/- hPSCs fail to differentiate into mesoderm or endoderm lineages. Unexpectedly, HS is dispensable for early ectodermal differentiation of hPSCs but still critical in generating motor neurons. Those derived from HS-deficient hPSCs lack proper neuronal projections and show alterations in axonogenesis gene expression. Thus, our study uncovers expected and unexpected mechanistic roles of HS in hPSC fate decisions.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102384"},"PeriodicalIF":5.9,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898280","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

Astrocyte-derived PTN alleviates deficits in hippocampal neurogenesis and cognition in models of multiple sclerosis. 星形胶质细胞衍生的PTN减轻多发性硬化症模型海马神经发生和认知的缺陷。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-01-14 Epub Date: 2024-12-26 DOI: 10.1016/j.stemcr.2024.11.013

Yanna Song, Haoyang Li, Yuhan Li, Huiming Xu, Faisal Hayat Nazir, Wei Jiang, Lu Zheng, Changyong Tang

{"title":"Astrocyte-derived PTN alleviates deficits in hippocampal neurogenesis and cognition in models of multiple sclerosis.","authors":"Yanna Song, Haoyang Li, Yuhan Li, Huiming Xu, Faisal Hayat Nazir, Wei Jiang, Lu Zheng, Changyong Tang","doi":"10.1016/j.stemcr.2024.11.013","DOIUrl":"10.1016/j.stemcr.2024.11.013","url":null,"abstract":"Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease that results in motor, sensory, cognitive, and affective deficits. Hippocampal demyelination, a common occurrence in MS, is linked to impaired cognitive function and mood. Despite this, the precise mechanisms underlying cognitive impairments in MS remain elusive. Pleiotrophin (PTN), secreted by neural stem cells and astrocytes, plays a crucial role in regulating cognition. This study investigates the role of astrocyte-derived PTN. We found that genetic deletion of astrocyte-derived PTN hinders hippocampal neurogenesis. Additionally, conditional ablation of PTN in astrocytes exacerbates neurogenic deficits in the demyelinated hippocampus. Importantly, overexpression of PTN in astrocytes reverses neurogenic and cognitive impairments caused by demyelination, underscoring PTN's protective role in MS. PTN cooperates with protein tyrosine phosphatase receptor type Z1 (PTPRZ1) or anaplastic lymphoma kinase (ALK) receptors to activate the AKT signaling pathway, thereby enhancing hippocampal neurogenesis and cognition in demyelinated mice. These findings illuminate novel effects of astrocyte-derived PTN on hippocampal neurogenesis and cognition.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102383"},"PeriodicalIF":5.9,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898277","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

Non-canonical roles of CFH in retinal pigment epithelial cells revealed by dysfunctional rare CFH variants. 功能失调的罕见CFH变异揭示了CFH在视网膜色素上皮细胞中的非规范作用。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-01-14 Epub Date: 2025-01-02 DOI: 10.1016/j.stemcr.2024.11.015

Sofie C A Brink, Louet Koolen, Caroline C W Klaver, Remko A Bakker, Anneke I den Hollander, Seba Almedawar

引用次数: 0

Optimized prime editing of the Alzheimer's disease-associated APOE4 mutation. 阿尔茨海默病相关APOE4突变的优化引物编辑。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-01-14 Epub Date: 2024-12-05 DOI: 10.1016/j.stemcr.2024.11.002

Antje K Rottner, Anders Lundin, Songyuan Li, Mike Firth, Marcello Maresca, Grzegorz Sienski

引用次数: 0

Low fucosylation defines the glycocalyx of progenitor cells and melanocytes in the human limbal stem cell niche. 在人角膜缘干细胞生态位中，低聚焦决定了祖细胞和黑素细胞的糖萼。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-01-14 Epub Date: 2024-12-19 DOI: 10.1016/j.stemcr.2024.11.008

Ashley M Woodward, Damien Guindolet, Rafael Martinez-Carrasco, Eric E Gabison, Robert M Lavker, Pablo Argüeso

{"title":"Low fucosylation defines the glycocalyx of progenitor cells and melanocytes in the human limbal stem cell niche.","authors":"Ashley M Woodward, Damien Guindolet, Rafael Martinez-Carrasco, Eric E Gabison, Robert M Lavker, Pablo Argüeso","doi":"10.1016/j.stemcr.2024.11.008","DOIUrl":"10.1016/j.stemcr.2024.11.008","url":null,"abstract":"It is widely recognized that the glycocalyx has significant implications in regulating the self-renewal and differentiation of adult stem cells; however, its composition remains poorly understood. Here, we show that the fucose-binding Aleuria aurantia lectin (AAL) binds differentially to basal cells in the stratified epithelium of the human limbus, hair follicle epithelium, and meibomian gland duct. Using fluorescence-activated cell sorting in combination with single-cell transcriptomics, we find that most epithelial progenitor cells and melanocytes in the limbus display low AAL staining (AALlow) on their cell surface, an attribute that is gradually lost in epithelial cells as they differentiate into mature corneal cells. AALlow epithelial cells were enriched in putative limbal stem cell markers and displayed high clonogenic capacity. Further analyses revealed that AALlow epithelial cells had reduced expression of GDP-mannose-4,6-dehydratase, an enzyme catalyzing the first and limiting step in the de novo biosynthesis of GDP-fucose, and that inhibition of fucosylation using a small-molecule fucose analog stimulated the proliferative potential of limbal epithelial cells ex vivo. These results provide crucial insights into the distinctive composition of the glycocalyx in adult stem cells and underscore the significance of fucose modulation in the therapeutic regeneration of the human limbal stem cell niche.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102378"},"PeriodicalIF":5.9,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872775","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

Swift induction of human spinal lower motor neurons and robust ALS cell screening via single-cell imaging. 通过单细胞成像快速诱导人类脊髓下运动神经元和强大的ALS细胞筛选。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-01-14 Epub Date: 2024-12-19 DOI: 10.1016/j.stemcr.2024.11.007

Selena Setsu, Satoru Morimoto, Shiho Nakamura, Fumiko Ozawa, Kagistia Hana Utami, Ayumi Nishiyama, Naoki Suzuki, Masashi Aoki, Yukio Takeshita, Yukihide Tomari, Hideyuki Okano

{"title":"Swift induction of human spinal lower motor neurons and robust ALS cell screening via single-cell imaging.","authors":"Selena Setsu, Satoru Morimoto, Shiho Nakamura, Fumiko Ozawa, Kagistia Hana Utami, Ayumi Nishiyama, Naoki Suzuki, Masashi Aoki, Yukio Takeshita, Yukihide Tomari, Hideyuki Okano","doi":"10.1016/j.stemcr.2024.11.007","DOIUrl":"10.1016/j.stemcr.2024.11.007","url":null,"abstract":"This study introduces a novel method for rapidly and efficiently inducing human spinal lower motor neurons (LMNs) from induced pluripotent stem cells (iPSCs) to eventually elucidate the pathomechanisms of amyotrophic lateral sclerosis (ALS) and facilitate drug screening. Previous methods were limited by low induction efficiency, poor LMN purity, or labor-intensive induction and evaluation processes. Our protocol overcomes these challenges, achieving around 80% induction efficiency within just two weeks by combining a small molecule-based approach with transcription factor transduction. Moreover, to exclude non-LMN cells from the analysis, we utilized time-lapse microscopy and machine learning to analyze the morphology and viability of iPSC-derived LMNs on a single-cell basis, establishing an effective pathophysiological evaluation system. This rapid, efficient, and streamlined protocol, along with our single-cell-based evaluation method, enables large-scale analysis and drug screening using iPSC-derived motor neurons.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102377"},"PeriodicalIF":5.9,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872829","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

Editorial. 社论。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-01-14 DOI: 10.1016/j.stemcr.2024.102390

Janet Rossant

引用次数: 0

Elevated hematopoietic stem cell frequency in mouse alveolar bone marrow. 小鼠肺泡骨髓中造血干细胞频率升高。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-01-14 Epub Date: 2024-12-12 DOI: 10.1016/j.stemcr.2024.11.004

Kouta Niizuma, Satoru Morikawa, Eric Gars, Jinyi Xiang, Tomoko Matsubara-Takahashi, Rei Saito, Eri Takematsu, Yuting Wang, Haojun Xu, Arata Wakimoto, Tze Kai Tan, Yoshiaki Kubota, Charles K F Chan, Irving L Weissman, Taneaki Nakagawa, Adam C Wilkinson, Hiromitsu Nakauchi, Ryo Yamamoto

{"title":"Elevated hematopoietic stem cell frequency in mouse alveolar bone marrow.","authors":"Kouta Niizuma, Satoru Morikawa, Eric Gars, Jinyi Xiang, Tomoko Matsubara-Takahashi, Rei Saito, Eri Takematsu, Yuting Wang, Haojun Xu, Arata Wakimoto, Tze Kai Tan, Yoshiaki Kubota, Charles K F Chan, Irving L Weissman, Taneaki Nakagawa, Adam C Wilkinson, Hiromitsu Nakauchi, Ryo Yamamoto","doi":"10.1016/j.stemcr.2024.11.004","DOIUrl":"10.1016/j.stemcr.2024.11.004","url":null,"abstract":"Hematopoietic stem cells (HSCs) are crucial for maintaining hematopoietic homeostasis and are localized within distinct bone marrow (BM) niches. While BM niches are often considered similar across different skeletal sites, we discovered that the alveolar BM (al-BM) in the mandible harbors the highest frequency of immunophenotypic HSCs in nine different skeletal sites. Transplantation assays revealed significantly increased engraftment from al-BM compared to femur, tibia, or pelvis BM, likely due to a higher proportion of alveolar HSCs. Moreover, hematopoietic progenitor cells (c-Kit+ Sca-1+ Lin-) in al-BM exhibited increased quiescence and reduced apoptosis, indicating superior maintenance and survival characteristics. We also observed an enrichment of mesenchymal stromal cells and skeletal stem cells in al-BM, suggesting a more supportive microenvironment. These findings indicate that al-BM provides a unique microenvironment conducive to higher frequency of HSCs, offering new insights into site-specific hematopoiesis.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102374"},"PeriodicalIF":5.9,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822703","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