Stem Cell Reports最新文献_第8页

Integrative analysis of drug-gene signatures in human pluripotent stem cells reveals prazosin as a novel SQSTM1 regulator for ALS therapeutics. 人类多能干细胞药物基因特征的综合分析显示，prazosin是ALS治疗的一种新的SQSTM1调节因子。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-07-14 Epub Date: 2026-06-25 DOI: 10.1016/j.stemcr.2026.102977

Florine Roussange, Jacqueline Gide, Johana Tournois, Michel Cailleret, Anne Boland, Christophe Battail, Jean-François Deleuze, Hélène Polvèche, Didier Auboeuf, Knut Brockmann, Edor Kabashi, Anca Marian, Lina El Kassar, Sophie Blondel, François Salachas, Gaëlle Bruneteau, Marc Peschanski, Cécile Martinat, Sandrine Baghdoyan

{"title":"Integrative analysis of drug-gene signatures in human pluripotent stem cells reveals prazosin as a novel SQSTM1 regulator for ALS therapeutics.","authors":"Florine Roussange, Jacqueline Gide, Johana Tournois, Michel Cailleret, Anne Boland, Christophe Battail, Jean-François Deleuze, Hélène Polvèche, Didier Auboeuf, Knut Brockmann, Edor Kabashi, Anca Marian, Lina El Kassar, Sophie Blondel, François Salachas, Gaëlle Bruneteau, Marc Peschanski, Cécile Martinat, Sandrine Baghdoyan","doi":"10.1016/j.stemcr.2026.102977","DOIUrl":"10.1016/j.stemcr.2026.102977","url":null,"abstract":"The classical paradigm of drug screening often faces significant limitations due to the challenges associated with identifying molecular or cellular read-outs that are relevant to specific genetic diseases. To remedy this, an alternative approach of reverse phenotypic mapping was tested: Compounds were evaluated for their effects on gene expression and alternative splicing in a healthy cell model, and the resulting data were matched to molecular signatures of diseases. A subset of 50 drugs was tested on mesenchymal stem cells derived from a human pluripotent stem cell line. Over half of the compounds altered gene expression, many affecting pathways linked to monogenic diseases. One hit, increased SQSTM1 expression induced by prazosin, was further validated in FTD/ALS type 3 models caused by SQSTM1 haploinsufficiency, including patient-derived fibroblasts, SQSTM1-depleted hiPSC-derived motor neurons, and a zebrafish model. Extending this paradigm could involve testing diverse cell types and larger drug libraries.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102977"},"PeriodicalIF":5.6,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148333282","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

Intravenous immunoglobulin enhances intestinal stem cell regeneration to mitigate radiation-induced enteritis via promoting β-catenin nuclear translocation. 静脉注射免疫球蛋白通过促进β-连环蛋白核易位促进肠道干细胞再生以减轻辐射诱导的肠炎。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-07-14 Epub Date: 2026-06-04 DOI: 10.1016/j.stemcr.2026.102934

Jia He, Tiancheng Chu, Ping Fu, Peng Jiang, Li Ma, Fengjuan Liu, Xi Du, Zhenni Xu, Jun Xu, Lu Cheng, Changqing Li, Dengqun Liu, Zongkui Wang

{"title":"Intravenous immunoglobulin enhances intestinal stem cell regeneration to mitigate radiation-induced enteritis via promoting β-catenin nuclear translocation.","authors":"Jia He, Tiancheng Chu, Ping Fu, Peng Jiang, Li Ma, Fengjuan Liu, Xi Du, Zhenni Xu, Jun Xu, Lu Cheng, Changqing Li, Dengqun Liu, Zongkui Wang","doi":"10.1016/j.stemcr.2026.102934","DOIUrl":"10.1016/j.stemcr.2026.102934","url":null,"abstract":"Radiation-induced enteritis (RIE), a common adverse effect after radiotherapy for pelvic, abdominal, and retroperitoneal tumors, has no effective treatment. Our previous study showed that intravenous immunoglobulin (IVIg) ameliorated radiation toxicity. Here, we investigated the role of IVIg in enhancing intestinal stem cell (ISC) regeneration to mitigate RIE and its underlying mechanism. In a mouse RIE model, IVIg improved tissue repair, reduced intestinal epithelial apoptosis and pyroptosis, decreased inflammatory factors, enhanced antioxidant capacity, and alleviated DNA damage. Notably, IVIg promoted the proliferation of OLFM4+ and LGR5+ ISCs in crypts and mitigated radiation-induced enteroid damage in vitro. Lineage tracing revealed that IVIg enhanced LGR5+ ISCs and their daughter cell survival. Mechanistically, IVIg promoted β-catenin nuclear translocation, and the β-catenin inhibitor MSAB diminished IVIg's radioprotective effects. Collectively, IVIg combats RIE by enhancing ISC regeneration via β-catenin nuclear translocation, highlighting its potential as an RIE therapeutic candidate.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102934"},"PeriodicalIF":5.6,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148164325","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

PCBP1 orchestrates amino acid metabolism burst during the naïve-to-primed pluripotency transition. 在naïve-to-primed多能性转变过程中，PCBP1协调氨基酸代谢爆发。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-07-14 Epub Date: 2026-06-04 DOI: 10.1016/j.stemcr.2026.102950

Evgeny I Bakhmet, Evgeniy V Potapenko, Oleg Y Shuvalov, Arseniy A Lobov, Egor A Repkin, Daria V Kriger, Nadezhda E Vorobyeva, Alexey N Korablev, Anna S Zinovyeva, Andrey A Kuzmin, Nikolay D Aksenov, Arthur T Kopylov, Guangming Wu, Hans R Schöler, Alexey N Tomilin

{"title":"PCBP1 orchestrates amino acid metabolism burst during the naïve-to-primed pluripotency transition.","authors":"Evgeny I Bakhmet, Evgeniy V Potapenko, Oleg Y Shuvalov, Arseniy A Lobov, Egor A Repkin, Daria V Kriger, Nadezhda E Vorobyeva, Alexey N Korablev, Anna S Zinovyeva, Andrey A Kuzmin, Nikolay D Aksenov, Arthur T Kopylov, Guangming Wu, Hans R Schöler, Alexey N Tomilin","doi":"10.1016/j.stemcr.2026.102950","DOIUrl":"10.1016/j.stemcr.2026.102950","url":null,"abstract":"Embryo implantation is accompanied by the naïve-to-primed pluripotency state transition in epiblast cells-the process involving proliferation and anabolic boost, needed for extensive embryo growth. Here, we show that Pcbp1 knockout leads to embryo growth arrest shortly after implantation. By modeling the naïve-to-primed pluripotency transition in vitro, we observe impaired proliferation and induction of apoptosis in cells deficient for PCBP1. Using multi-omics approaches, we reveal a crucial role for PCBP1 in driving a transcriptional burst of numerous genes involved in the import and the de novo synthesis of essential and conditionally essential amino acids. PCBP1 deficiency is consequently associated with a slowdown in protein biosynthesis, which explains the early lethality of the knockout embryos. Our findings thus uncover the molecular mechanisms underlying anabolic changes during the naïve-to-primed pluripotency transition and highlight the essential role of PCBP1 in this critical process.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102950"},"PeriodicalIF":5.6,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148164305","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

Pro-repair properties of a human embryonic stem cell-derived astrocyte cell therapy in demyelinating disorders. 人类胚胎干细胞来源的星形胶质细胞治疗脱髓鞘疾病的促修复特性。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-07-14 Epub Date: 2026-06-11 DOI: 10.1016/j.stemcr.2026.102960

Lihi Sofer Stepanov, Nina Fainstein, Marva Lachish, Tal Ganz, Yoel Shor, Gal Lebiush Shalom, Shir Klein-Lavi, Michal Izrael, Debora Steiner, Benjamin E Reubinoff, Michel Revel, Tamir Ben-Hur

{"title":"Pro-repair properties of a human embryonic stem cell-derived astrocyte cell therapy in demyelinating disorders.","authors":"Lihi Sofer Stepanov, Nina Fainstein, Marva Lachish, Tal Ganz, Yoel Shor, Gal Lebiush Shalom, Shir Klein-Lavi, Michal Izrael, Debora Steiner, Benjamin E Reubinoff, Michel Revel, Tamir Ben-Hur","doi":"10.1016/j.stemcr.2026.102960","DOIUrl":"10.1016/j.stemcr.2026.102960","url":null,"abstract":"Remyelination failure in demyelinating diseases is driven by inefficient myelin debris clearance, impaired oligodendrocyte progenitor cell (OPC) differentiation into mature oligodendrocytes, and the absence of a sustained pro-repair inflammatory environment. Effective remyelination requires a pro-repair inflammatory environment that supports myelin debris removal and promotes OPC maturation. We examined whether AstroRx, a clinical-grade human embryonic stem cell (hESC)-derived astrocyte therapy, addresses these barriers. In co-cultures in-vitro, AstroRx enhanced microglial phagocytosis of myelin debris, extended lymphocyte proliferation, and survival without excessive activation, and enhanced murine and hESC-derived OPC differentiation. In a lysolecithin-induced demyelination model in-vivo, intraventricular-delivered AstroRx promoted microglial-mediated myelin debris clearance and oligodendrogenesis in the peri-lesion white matter. These findings demonstrate that AstroRx sustains a pro-repair effect via a bystander mechanism, maintaining an inflammatory milieu, facilitating myelin debris removal, and oligodendrogenesis. With demonstrated clinical safety, scalability, and multi-targeted reparative effects, AstroRx offers a promising off-the-shelf cell therapy for chronic demyelination.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102960"},"PeriodicalIF":5.6,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148228538","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

HDAC4 regulates hASC osteogenesis and bone regeneration by mediating SMAD4 via histone acetylation. HDAC4通过组蛋白乙酰化介导SMAD4调控hASC成骨和骨再生。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-07-14 Epub Date: 2026-06-11 DOI: 10.1016/j.stemcr.2026.102955

Liyuan Yu, Kai Xia, Yijue Wang, Zhiai Hu, Jun Liu, Shujuan Zou, Jianwei Chen

引用次数: 0

Rat cell-derived kidney generation via interspecies blastocyst complementation in an Osr1-KO mouse model. 在Osr1-KO小鼠模型中，通过种间囊胚互补产生大鼠细胞来源的肾脏。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-07-14 Epub Date: 2026-06-11 DOI: 10.1016/j.stemcr.2026.102957

Shunsuke Yuri, Ayako Isotani

引用次数: 0

Allogeneic islet products for type 1 diabetes: Navigating nonclinical and manufacturing regulatory expectations. 治疗1型糖尿病的同种异体胰岛产品：引导非临床和生产监管期望。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-07-14 Epub Date: 2026-07-06 DOI: 10.1016/j.stemcr.2026.102998

Chengyuan Press, Kevin D'Amour, Nicholas Mamrak, David Pepperl, Robert H Kutner, Diana M Colleluori, Melanie L Graham, Michael A Brehm, Nasir Hussain, Esther Latres, Marjana Marinac

引用次数: 0

Rewiring ALS by modulating the autophagy receptor SQSTM1. 通过调节自噬受体SQSTM1重新布线ALS。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-07-14 Epub Date: 2026-06-25 DOI: 10.1016/j.stemcr.2026.102976

Laetitia Aubry, Viktor I Korolchuk, Sovan Sarkar

引用次数: 0

CD157⁺ vascular endothelial stem cells represent a conserved subpopulation with an angiogenic gene expression profile. CD157+血管内皮干细胞代表了一个保守的亚群，具有血管生成基因表达谱。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-07-14 Epub Date: 2026-06-04 DOI: 10.1016/j.stemcr.2026.102931

Tomohiro Iba, Taku Wakabayashi, Rie Ito, Ai Sugawara, Satoshi Fujimura, Mika Sawane, Kazuaki Yoshioka, Aya Matsui, Jun-Ichi Morishige, Naoto Nagata, Yukinobu Ito, Masafumi Horie, Daichi Maeda, Rica Tanaka, Hitoshi Ando, Nobuyuki Takakura, Hisamichi Naito

{"title":"CD157+ vascular endothelial stem cells represent a conserved subpopulation with an angiogenic gene expression profile.","authors":"Tomohiro Iba, Taku Wakabayashi, Rie Ito, Ai Sugawara, Satoshi Fujimura, Mika Sawane, Kazuaki Yoshioka, Aya Matsui, Jun-Ichi Morishige, Naoto Nagata, Yukinobu Ito, Masafumi Horie, Daichi Maeda, Rica Tanaka, Hitoshi Ando, Nobuyuki Takakura, Hisamichi Naito","doi":"10.1016/j.stemcr.2026.102931","DOIUrl":"10.1016/j.stemcr.2026.102931","url":null,"abstract":"Endothelial cells expressing the CD157 antigen (CD157+ ECs) contribute to vascular regeneration and maintenance in adult tissues, but their molecular identity is not fully defined. Here, we show that CD157-positive ECs in mouse and human tissues share conserved transcriptional profiles enriched for angiogenesis-associated genes. Regulon analysis revealed a gene-regulatory network in which the NFAT pathway contributes to vascular network formation. Integration of mouse and human scRNA-seq datasets revealed human EC clusters with gene expression profiles resembling mouse CD157-positive ECs. The clusters were localized in the large vessel intima and expressed known stem-like EC markers such as BST1 (CD157), PROCR (CD201), and ABCG2. Functionally, human CD157+ ECs isolated from muscle exhibited greater proliferative capacity than CD157- ECs. Cell-cell interaction analysis suggested active communication between CD157-positive ECs and surrounding cells, via the CXCL12-CXCR7 axis. Our findings identify a conserved gene signature for CD157+ ECs with potential relevance for vascular regeneration.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102931"},"PeriodicalIF":5.6,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148164337","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

Aging of hematopoietic stem cells is inconsequential to progenitor cell function. 造血干细胞的衰老与祖细胞的功能无关。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-07-14 Epub Date: 2026-06-18 DOI: 10.1016/j.stemcr.2026.102965

Jenna Myers, Atesh K Worthington, Donna M Poscablo, Paloma Medina, Saran Chattopadhyaya, Raana Mogharrab, Marcel G E Rommel, E Camilla Forsberg

{"title":"Aging of hematopoietic stem cells is inconsequential to progenitor cell function.","authors":"Jenna Myers, Atesh K Worthington, Donna M Poscablo, Paloma Medina, Saran Chattopadhyaya, Raana Mogharrab, Marcel G E Rommel, E Camilla Forsberg","doi":"10.1016/j.stemcr.2026.102965","DOIUrl":"10.1016/j.stemcr.2026.102965","url":null,"abstract":"Aging of the hematopoietic system has profound consequences for organismal health and longevity, attributed to the well-characterized functional aging of hematopoietic stem cells (HSCs). Here, we tested whether progenitor cells may demonstrate age resistance to enable hematopoietic homeostasis throughout life despite the functional decline of upstream HSCs. Strikingly, our results revealed unwavering reconstitution capacity by young and old progenitors, demonstrating that intermediate progenitors are functionally unaffected by aging and placing Flk2+ multipotent progenitors (MPPFs) as a potential source of age resilience. This unique finding was emphasized by unchanged transcriptomic, proliferation, and mitochondrial capacity of young and old MPPFs, revealing remarkable similarities upon aging. Considering that HSCs functionally decline with age, yet intermediate progenitors remain unperturbed and \"age resilient\", we posit that MPPFs may play an essential role in protecting downstream progenitors from inheriting age-related properties from HSCs. We propose three potential mechanisms for how MPPFs maintain hematopoietic integrity and homeostasis with age.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102965"},"PeriodicalIF":5.6,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148278801","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