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Cardiopedia-Ligand: A ligand-receptor perturbation atlas of human cardiac organoid function and transcriptional state. 心脏配体:人类心脏类器官功能和转录状态的配体-受体摄动图谱。
IF 20.4
Cell stem cell Pub Date : 2026-08-06 Epub Date: 2026-07-28 DOI: 10.1016/j.stem.2026.07.004
Janice D Reid, Simon R Foster, Mary Lor, Alexander S Hauser, Brendan Griffen, Rebecca L Fitzsimmons, James E Hudson
{"title":"Cardiopedia-Ligand: A ligand-receptor perturbation atlas of human cardiac organoid function and transcriptional state.","authors":"Janice D Reid, Simon R Foster, Mary Lor, Alexander S Hauser, Brendan Griffen, Rebecca L Fitzsimmons, James E Hudson","doi":"10.1016/j.stem.2026.07.004","DOIUrl":"10.1016/j.stem.2026.07.004","url":null,"abstract":"<p><p>Large-scale perturbation atlases have transformed systems biology, yet no equivalent resource exists for the human heart, where contractile function and transcriptomic state must be measured together. Here, we establish Cardiopedia-Ligand, a comprehensive perturbation-function-transcriptome atlas generated by stimulating human cardiac organoids (hCOs) with 87 ligands targeting 98 cell-membrane receptors expressed in the human heart. We developed an automated high-throughput pipeline enabling individualized contractility measurements and single-organoid mRNA sequencing. We use this pipeline to define both recognized and previously unrecognized functional and transcriptional clusters, including inotropes, endothelin peptides, extracellular matrix regulators, and multiple inflammatory clusters. Clustering analysis, machine learning, and the \"fingerprinting\" of human heart failure biopsies revealed previously underappreciated similarities between ligands and an interferon-γ signaling signature driving heart failure with preserved ejection fraction (HFpEF). Together, this comprehensive Cardiopedia-Ligand dataset provides a valuable and accessible resource for interrogating cardiac biology and human disease.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"1363-1378.e9"},"PeriodicalIF":20.4,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148611035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Living therapeutic depots: Matching design to therapeutic needs. 生活治疗仓库:将设计与治疗需求相匹配。
IF 20.4
Cell stem cell Pub Date : 2026-08-06 DOI: 10.1016/j.stem.2026.07.009
Han Zhou, Qirui Liang, Yucai Wang
{"title":"Living therapeutic depots: Matching design to therapeutic needs.","authors":"Han Zhou, Qirui Liang, Yucai Wang","doi":"10.1016/j.stem.2026.07.009","DOIUrl":"10.1016/j.stem.2026.07.009","url":null,"abstract":"<p><p>Living therapeutic depots enable localized, adaptive therapy, but their success depends on persistence, activation, and therapeutic output. Harimoto et al.<sup>1</sup> define mechanical requirements for durable bacterial containment, whereas Luo et al.<sup>2</sup> integrate transient photosynthetic hydrogen production with cardiac therapy. Together, the studies demonstrate that therapeutic needs shape living therapeutic design.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":"33 8","pages":"1254-1256"},"PeriodicalIF":20.4,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148687102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reconstructing primate gametogenesis along its developmental trajectory. 沿发育轨迹重建灵长类配子发生。
IF 20.4
Cell stem cell Pub Date : 2026-08-06 Epub Date: 2026-07-23 DOI: 10.1016/j.stem.2026.07.006
Shosei Yoshida
{"title":"Reconstructing primate gametogenesis along its developmental trajectory.","authors":"Shosei Yoshida","doi":"10.1016/j.stem.2026.07.006","DOIUrl":"10.1016/j.stem.2026.07.006","url":null,"abstract":"<p><p>Using a xenogeneic reconstituted testis transplanted beneath the kidney capsule, Whelan et al. advance human and rhesus macaque pluripotent stem cell-derived germ cells beyond fetal prospermatogonia.<sup>1</sup> Their study highlights developmental time, niche organization, and lineage history as central challenges for reconstructing faithful primate gametogenesis.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"1249-1251"},"PeriodicalIF":20.4,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Extracellular vesicle secretome from mesenchymal stromal cells prevents post-ischemic heart failure by targeting cardiac fibrosis. 间充质间质细胞的胞外囊泡分泌组通过靶向心脏纤维化预防缺血性心力衰竭。
IF 20.4
Cell stem cell Pub Date : 2026-08-06 Epub Date: 2026-07-24 DOI: 10.1016/j.stem.2026.07.003
Karl-Henrik Grinnemo, Ken Braesch-Andersen, Johan O Wedin, Anna Velica, Ulrika Thelander, Pierre Sabatier, Christian M Beusch, Oscar E Simonson, Alice Törne, Ulrika Felldin, Olga Gritsenko, Kyong-Su Park, Rossella Crescitelli, Nils Ågren, Stephan Meinke, Ayman Abouzayed, Olivia Wegrzyniak, Andriana Putri, Patricia Hedenqvist, Anneli Rydén, Alexandra Leijon, Lisa Lindström, Irina Velikyan, Evren Alici, Johannes Wikström, Li Ming Gan, Tomas Lorant, Makiko Kumagai-Braesch, Elisabeth Ståhle, Olle Korsgren, Karin Fromell, Kristina Nilsson-Ekdahl, Bo Nilsson, Jan Lötvall, Marianne Jensen-Waern, Jesper V Olsen, Daniel W Hagey, Samir E L Andaloussi, Katarina Le Blanc, Stefan James, Olof Eriksson, Sergey Rodin
{"title":"Extracellular vesicle secretome from mesenchymal stromal cells prevents post-ischemic heart failure by targeting cardiac fibrosis.","authors":"Karl-Henrik Grinnemo, Ken Braesch-Andersen, Johan O Wedin, Anna Velica, Ulrika Thelander, Pierre Sabatier, Christian M Beusch, Oscar E Simonson, Alice Törne, Ulrika Felldin, Olga Gritsenko, Kyong-Su Park, Rossella Crescitelli, Nils Ågren, Stephan Meinke, Ayman Abouzayed, Olivia Wegrzyniak, Andriana Putri, Patricia Hedenqvist, Anneli Rydén, Alexandra Leijon, Lisa Lindström, Irina Velikyan, Evren Alici, Johannes Wikström, Li Ming Gan, Tomas Lorant, Makiko Kumagai-Braesch, Elisabeth Ståhle, Olle Korsgren, Karin Fromell, Kristina Nilsson-Ekdahl, Bo Nilsson, Jan Lötvall, Marianne Jensen-Waern, Jesper V Olsen, Daniel W Hagey, Samir E L Andaloussi, Katarina Le Blanc, Stefan James, Olof Eriksson, Sergey Rodin","doi":"10.1016/j.stem.2026.07.003","DOIUrl":"10.1016/j.stem.2026.07.003","url":null,"abstract":"<p><p>Myocardial ischemia-reperfusion (MIR) injury drives adverse remodeling and heart failure after ST-elevation myocardial infarction (STEMI), yet no therapy directly targets the fibrotic response. Here, we developed a good manufacturing practice-compatible extracellular vesicle (EV)-enriched secretome from bone marrow mesenchymal stromal cells and identified a laminin-521-based production strategy suitable for clinical translation. The EV-enriched secretome exhibited in vitro immunomodulatory activity, and in murine MIR-injury models, treatment preserved left ventricular ejection fraction, reduced platelet-derived growth factor receptor beta (PDGFRβ)-associated myofibroblast activation quantified by positron emission tomography (PET) imaging, attenuated fibrosis, and promoted reparative macrophage polarization. In a clinically relevant porcine ischemia-reperfusion model, intracoronary administration was cardioprotective. We further developed a clinically approved PDGFRβ-targeted PET-imaging platform for longitudinal assessment of fibrotic activity in STEMI patients, where preliminary observations suggest that myofibroblast activation persists for up to 2 months after STEMI in selected patients. Together, these findings establish a translational therapeutic-diagnostic framework for individualized management of MIR injury.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"1324-1338.e10"},"PeriodicalIF":20.4,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148586265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Patient-derived organoids reveal ductal dysfunction and CFTR-modulator responses in chronic pancreatitis. 慢性胰腺炎患者来源的类器官显示导管功能障碍和cftr调节反应。
IF 20.4
Cell stem cell Pub Date : 2026-08-06 Epub Date: 2026-06-30 DOI: 10.1016/j.stem.2026.06.002
Victoria Osorio-Vasquez, Jonathan Zhu, Jan C Lumibao, Kathryn Lande, Kristina L Peck, McKenna K Stamp, Shira R Okhovat, Hyemin Song, Satoshi Ogawa, Casie S Kubota, Vasiliki Pantazopoulou, Kassidy Curtis, Kahing Kuo, Yang Dai, Angelica Rock, Chelsea R Bottomley, Ethan J Thomas, Jasper Hsu, Araceli Herrera Morales, Alexandra Fowler, T'Onj McGriff, K Garrett Evensen, April E Williams, Siri Larsen, Muhamad Abdulla, Phil Greer, Jessica Gibson, Michael Downes, Ronald M Evans, Andrew M Lowy, David C Whitcomb, Jingjing Zou, Alfredo Molinolo, Tae Gyu Oh, Rebekah R White, Melena Bellin, Hervé Tiriac, Dannielle D Engle
{"title":"Patient-derived organoids reveal ductal dysfunction and CFTR-modulator responses in chronic pancreatitis.","authors":"Victoria Osorio-Vasquez, Jonathan Zhu, Jan C Lumibao, Kathryn Lande, Kristina L Peck, McKenna K Stamp, Shira R Okhovat, Hyemin Song, Satoshi Ogawa, Casie S Kubota, Vasiliki Pantazopoulou, Kassidy Curtis, Kahing Kuo, Yang Dai, Angelica Rock, Chelsea R Bottomley, Ethan J Thomas, Jasper Hsu, Araceli Herrera Morales, Alexandra Fowler, T'Onj McGriff, K Garrett Evensen, April E Williams, Siri Larsen, Muhamad Abdulla, Phil Greer, Jessica Gibson, Michael Downes, Ronald M Evans, Andrew M Lowy, David C Whitcomb, Jingjing Zou, Alfredo Molinolo, Tae Gyu Oh, Rebekah R White, Melena Bellin, Hervé Tiriac, Dannielle D Engle","doi":"10.1016/j.stem.2026.06.002","DOIUrl":"10.1016/j.stem.2026.06.002","url":null,"abstract":"<p><p>Chronic pancreatitis (CP) affects ∼3 million people worldwide, yet altering the course of the disease is challenging. We developed a patient-derived organoid (PDO) platform to investigate the molecular pathogenesis of this disease and identify therapeutic strategies. We generated 37 PDOs from patients with idiopathic, hereditary, and alcohol-related CP with a high genetic concordance. PDOs retained inflammation-associated transcriptional and proteomic features. Transcriptomic profiling revealed three molecular subtypes of CP independent of etiology. We discovered widespread dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) in half of the CP PDOs, including those with wild-type CFTR. Clinically available CFTR modulators stabilized mutant or wild-type CFTR, restored CFTR function, and decreased mitogenic and inflammatory signaling. This work provides a comprehensive PDO platform for modeling CP. We demonstrate the utility of this platform for precision therapeutic investigations. Our findings reveal CFTR modulators as a broadly applicable and effective therapeutic strategy.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"1270-1288.e7"},"PeriodicalIF":20.4,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13477807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148364422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
SPACE-seq integrates spatial transcriptomics and lineage tracing in native tissues. SPACE-seq整合了本地组织的空间转录组学和谱系追踪。
IF 20.4
Cell stem cell Pub Date : 2026-08-06 Epub Date: 2026-06-09 DOI: 10.1016/j.stem.2026.05.017
Yuemeng Jia, Dawei Sun, Jackson A Weir, Xugeng Liu, Andrew J C Russell, YeEun Kim, Nicholas Thom, Giovanni Marrero, Vipin Kumar, Fei Chen, Fernando D Camargo
{"title":"SPACE-seq integrates spatial transcriptomics and lineage tracing in native tissues.","authors":"Yuemeng Jia, Dawei Sun, Jackson A Weir, Xugeng Liu, Andrew J C Russell, YeEun Kim, Nicholas Thom, Giovanni Marrero, Vipin Kumar, Fei Chen, Fernando D Camargo","doi":"10.1016/j.stem.2026.05.017","DOIUrl":"10.1016/j.stem.2026.05.017","url":null,"abstract":"<p><p>Understanding how cells change state, interact with their neighbors, and organize into tissues requires recording of cellular lineage history in native spatial context. Here, we present SPACE-seq (spatial tracing enabled by CRISPR-based barcodes and slide-seq), a versatile platform that integrates CRISPR-based lineage recording with spatial transcriptomics to jointly resolve lineage, cell state, and tissue architecture at near-cellular resolution in situ. Using SPACE-seq, we uncovered intratumor transcriptional diversification among clonally related cells and identified tumor-stroma crosstalk that reciprocally reshapes behaviors of both malignant and stromal populations, which we further experimentally validated. Beyond disease, SPACE-seq revealed a narrow developmental window in which hepatoblast dispersion contributes to spatially confined lineage compartments that prefigure liver lobar architecture. Together, these results highlight the broad applicability and adaptability of SPACE-seq to uncover previously inaccessible principles of cellular organization, lineage dynamics, and tissue patterning.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"1398-1413.e10"},"PeriodicalIF":20.4,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148213682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The price of plasticity: Losing colon identity to gain metastatic potential. 可塑性的代价:失去结肠的特性以获得转移的潜力。
IF 20.4
Cell stem cell Pub Date : 2026-08-06 DOI: 10.1016/j.stem.2026.07.005
Bianca Băloiu, Hugo J G Snippert
{"title":"The price of plasticity: Losing colon identity to gain metastatic potential.","authors":"Bianca Băloiu, Hugo J G Snippert","doi":"10.1016/j.stem.2026.07.005","DOIUrl":"10.1016/j.stem.2026.07.005","url":null,"abstract":"<p><p>The generation of highly plastic cell states in colorectal cancer that are prone to metastatic dissemination involves complex epigenetic reprogramming, rather than new genetic traits. Goto et al.<sup>1</sup> implement a serial orthotopic organoid transplantation framework to uncover the idea that losing Gata6, a guardian of the colonic lineage, promotes metastatic competence.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":"33 8","pages":"1246-1248"},"PeriodicalIF":20.4,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148687066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
"Heart-in-the-dish" models identify mechanisms of diastolic dysfunction. “盘中心脏”模型确定了舒张功能障碍的机制。
IF 20.4
Cell stem cell Pub Date : 2026-08-06 DOI: 10.1016/j.stem.2026.07.007
Gesine M Dittrich, Wolfram-Hubertus Zimmermann
{"title":"\"Heart-in-the-dish\" models identify mechanisms of diastolic dysfunction.","authors":"Gesine M Dittrich, Wolfram-Hubertus Zimmermann","doi":"10.1016/j.stem.2026.07.007","DOIUrl":"10.1016/j.stem.2026.07.007","url":null,"abstract":"<p><p>Modeling of cardiac pathologies in tissue-engineered models is coming of age. Two independent studies by Reid et al.<sup>1</sup> and Tani et al.<sup>2</sup> present in-depth multi-phenomics data from a human cardiac organoid (hCO) model and explore hCOs and engineered heart tissues (EHTs) for modeling of diastolic dysfunction.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":"33 8","pages":"1243-1245"},"PeriodicalIF":20.4,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148687048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dissecting divergent outcomes in stem cell-derived dopamine cell therapy trials for Parkinson's disease. 干细胞来源的多巴胺细胞治疗帕金森病试验的不同结果
IF 20.4
Cell stem cell Pub Date : 2026-08-06 Epub Date: 2026-07-24 DOI: 10.1016/j.stem.2026.07.002
Chan Wook Park, Sanghyun Park, Seok Jong Chung, Phil Hyu Lee, Dong-Wook Kim
{"title":"Dissecting divergent outcomes in stem cell-derived dopamine cell therapy trials for Parkinson's disease.","authors":"Chan Wook Park, Sanghyun Park, Seok Jong Chung, Phil Hyu Lee, Dong-Wook Kim","doi":"10.1016/j.stem.2026.07.002","DOIUrl":"10.1016/j.stem.2026.07.002","url":null,"abstract":"<p><p>Fetal tissue transplantation established proof-of-concept for dopamine cell replacement in Parkinson's disease but yielded inconsistent outcomes due to limited tissue availability and cellular heterogeneity. Advances in generating high-purity dopamine progenitors from pluripotent stem cells have enabled standardized products that show safety and motor improvement in clinical trials. However, these trials revealed divergent outcomes arising at three levels: between clinical studies, driven by differences in cell products, baseline patient characteristics, or immunosuppressants; between patients, influenced by alloimmune factors, genetic background, or co-pathology; and within patients, where graft survival varies across transplantation sites due to the local microenvironment or surgical technique.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"1257-1269"},"PeriodicalIF":20.4,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148586248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mapping cell fate in space and time. 绘制细胞在空间和时间上的命运。
IF 20.4
Cell stem cell Pub Date : 2026-08-06 DOI: 10.1016/j.stem.2026.07.001
Hannah Stuart, Aaron McKenna
{"title":"Mapping cell fate in space and time.","authors":"Hannah Stuart, Aaron McKenna","doi":"10.1016/j.stem.2026.07.001","DOIUrl":"10.1016/j.stem.2026.07.001","url":null,"abstract":"<p><p>Cellular development unfolds across both space and time, with lineage history influencing cellular identity and tissue organization. In this issue of Cell Stem Cell, Jia et al.<sup>1</sup> combine CRISPR lineage recording with spatial transcriptomics to reconstruct the clonal relationships and spatial organization of cells during mouse development and cancer progression.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":"33 8","pages":"1252-1253"},"PeriodicalIF":20.4,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148687078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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