Stem Cell Reports最新文献_第2页

A versatile in vivo platform for reversible control of transgene expression in adult tissues. 一个多功能的体内平台可逆控制转基因表达在成人组织。

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.2024.11.003

Jumpei Taguchi, Yosuke Yamada, Sho Ohta, Fumie Nakasuka, Takuya Yamamoto, Manabu Ozawa, Yasuhiro Yamada

{"title":"A versatile in vivo platform for reversible control of transgene expression in adult tissues.","authors":"Jumpei Taguchi, Yosuke Yamada, Sho Ohta, Fumie Nakasuka, Takuya Yamamoto, Manabu Ozawa, Yasuhiro Yamada","doi":"10.1016/j.stemcr.2024.11.003","DOIUrl":"10.1016/j.stemcr.2024.11.003","url":null,"abstract":"Temporal control of transgenes has advanced biomedical interventions, including in vivo reprogramming, often utilizing the doxycycline (Dox)-mediated Tet-ON system. Here, we developed the Dox-mediated Tet-ON or complementary Tet-OFF counterpart to thoroughly investigate spatial and temporal transgene regulation in adult tissues, revealing inherent limitations and unexpected capabilities of each system. In stark contrast with the Tet-ON system, which was effective only in particular tissues and cell types, primarily epithelial cells, the Tet-OFF system proved capable of gene induction across diverse cell types. Despite the drawback of the Tet-OFF system in inducibility and tunability identified in our study, we demonstrated that use of tetracycline (Tc) effectively addresses these issues, possibly through its pharmacologic properties. Our data suggest that the Tc-mediated Tet-OFF system not only enables more versatile control of transgene expression but also offers a more biocompatible alternative for in vivo applications such as tissue regeneration and organismal rejuvenation.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102373"},"PeriodicalIF":5.9,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791708","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

Engineering the 3D structure of organoids. 设计类器官的三维结构。

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.2024.11.009

Samuel P Moss, Ezgi Bakirci, Adam W Feinberg

引用次数: 0

Nascent matrix deposition supports alveolar organoid formation from aggregates in synthetic hydrogels. 新生基质沉积支持合成水凝胶聚集体形成肺泡类器官。

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.2024.11.006

Madeline K Eiken, Charlie J Childs, Lindy K Brastrom, Tristan Frum, Eleanor M Plaster, Donia W Ahmed, Ryan C Spencer, Orren Shachaf, Suzanne Pfeiffer, Justin E Levine, Konstantinos-Dionysios Alysandratos, Darrell N Kotton, Jason R Spence, Claudia Loebel

{"title":"Nascent matrix deposition supports alveolar organoid formation from aggregates in synthetic hydrogels.","authors":"Madeline K Eiken, Charlie J Childs, Lindy K Brastrom, Tristan Frum, Eleanor M Plaster, Donia W Ahmed, Ryan C Spencer, Orren Shachaf, Suzanne Pfeiffer, Justin E Levine, Konstantinos-Dionysios Alysandratos, Darrell N Kotton, Jason R Spence, Claudia Loebel","doi":"10.1016/j.stemcr.2024.11.006","DOIUrl":"10.1016/j.stemcr.2024.11.006","url":null,"abstract":"Human induced pluripotent stem cell (iPSC)-derived alveolar organoids have emerged as a system to model the alveolar epithelium in homeostasis and disease. However, alveolar organoids are typically grown in Matrigel, a mouse sarcoma-derived basement membrane matrix that offers poor control over matrix properties, prompting the development of synthetic hydrogels as a Matrigel alternative. Here, we develop a two-step culture method that involves pre-aggregation of organoids in hydrogel-based microwells followed by embedding in a synthetic hydrogel that supports alveolar organoid growth, while also offering considerable control over organoid and hydrogel properties. We find that the aggregated organoids secrete their own nascent extracellular matrix (ECM) both in the microwells and upon embedding in synthetic hydrogels, which supports their growth. Thus, the synthetic hydrogels described here allow us to de-couple exogenous and nascent ECM to interrogate the role of ECM in organoid formation.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102376"},"PeriodicalIF":5.9,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822704","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

Exploiting O-GlcNAc dyshomeostasis to screen O-GlcNAc transferase intellectual disability variants. 利用O-GlcNAc失衡筛选O-GlcNAc转移酶智力残疾变异。

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.2024.11.010

Huijie Yuan, Conor W Mitchell, Andrew T Ferenbach, Maria Teresa Bonati, Agnese Feresin, Paul J Benke, Queenie K G Tan, Daan M F van Aalten

{"title":"Exploiting O-GlcNAc dyshomeostasis to screen O-GlcNAc transferase intellectual disability variants.","authors":"Huijie Yuan, Conor W Mitchell, Andrew T Ferenbach, Maria Teresa Bonati, Agnese Feresin, Paul J Benke, Queenie K G Tan, Daan M F van Aalten","doi":"10.1016/j.stemcr.2024.11.010","DOIUrl":"10.1016/j.stemcr.2024.11.010","url":null,"abstract":"O-GlcNAcylation is an essential protein modification catalyzed by O-GlcNAc transferase (OGT). Missense variants in OGT are linked to a novel intellectual disability syndrome known as OGT congenital disorder of glycosylation (OGT-CDG). The mechanisms by which OGT missense variants lead to this heterogeneous syndrome are not understood, and no unified method exists for dissecting pathogenic from non-pathogenic variants. Here, we develop a double-fluorescence strategy in mouse embryonic stem cells to measure disruption of O-GlcNAc homeostasis by quantifying the effects of variants on endogenous OGT expression. OGT-CDG variants generally elicited a lower feedback response than wild-type and Genome Aggregation Database (gnomAD) OGT variants. This approach was then used to dissect new putative OGT-CDG variants from pathogenic background variants in other disease-associated genes. Our work enables the prediction of pathogenicity for rapidly emerging de novo OGT-CDG variants and points to reduced disruption of O-GlcNAc homeostasis as a common mechanism underpinning OGT-CDG.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102380"},"PeriodicalIF":5.9,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872772","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

Chemically defined and growth factor-free system for highly efficient endoderm induction of human pluripotent stem cells. 化学定义的无生长因子系统，用于高效的人多能干细胞内胚层诱导。

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.2024.11.012

Zhiju Zhao, Fanzhu Zeng, Yage Nie, Gang Lu, He Xu, He En, Shanshan Gu, Wai-Yee Chan, Nan Cao, Jia Wang

{"title":"Chemically defined and growth factor-free system for highly efficient endoderm induction of human pluripotent stem cells.","authors":"Zhiju Zhao, Fanzhu Zeng, Yage Nie, Gang Lu, He Xu, He En, Shanshan Gu, Wai-Yee Chan, Nan Cao, Jia Wang","doi":"10.1016/j.stemcr.2024.11.012","DOIUrl":"10.1016/j.stemcr.2024.11.012","url":null,"abstract":"Definitive endoderm (DE) derived from human pluripotent stem cells (hPSCs) holds great promise for cell-based therapies and drug discovery. However, current DE differentiation methods required undefined components and/or expensive recombinant proteins, limiting their scalable manufacture and clinical use. Homogeneous DE differentiation in defined and recombinant protein-free conditions remains a major challenge. Here, by systematic optimization and high-throughput screening, we report a chemically defined, small-molecule-based defined system that contains only four components (4C), enabling highly efficient and cost-effective DE specification of hPSCs in the absence of recombinant proteins. 4C-induced DE can differentiate into functional hepatocytes, lung epithelium, and pancreatic β cells in vitro and multiple DE derivatives in vivo. Genomic accessibility analysis reveals that 4C reconfigures chromatin architecture to allow key DE transcription factor binding while identifying TEAD3 as a novel key regulator of the process. This system may facilitate mass production of DE derivatives for drug discovery, disease modeling, and cell therapy.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102382"},"PeriodicalIF":5.9,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898279","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

Efficient differentiation of human iPSCs into Leydig-like cells capable of long-term stable secretion of testosterone. 人多能干细胞有效分化为能够长期稳定分泌睾酮的leydigi样细胞。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-01-13 DOI: 10.1016/j.stemcr.2024.102392

Katsuya Sato, Michiyo Koyanagi-Aoi, Keiichiro Uehara, Yosuke Yamashita, Masakazu Shinohara, Suji Lee, Anika Reinhardt, Knut Woltjen, Koji Chiba, Hideaki Miyake, Masato Fujisawa, Takashi Aoi

{"title":"Efficient differentiation of human iPSCs into Leydig-like cells capable of long-term stable secretion of testosterone.","authors":"Katsuya Sato, Michiyo Koyanagi-Aoi, Keiichiro Uehara, Yosuke Yamashita, Masakazu Shinohara, Suji Lee, Anika Reinhardt, Knut Woltjen, Koji Chiba, Hideaki Miyake, Masato Fujisawa, Takashi Aoi","doi":"10.1016/j.stemcr.2024.102392","DOIUrl":"https://doi.org/10.1016/j.stemcr.2024.102392","url":null,"abstract":"Late-onset hypogonadism (LOH) syndrome is characterized by age-related testosterone deficiency and negatively affects the quality of life of older men. A promising therapeutic approach for LOH syndrome is transplantation of testosterone-producing Leydig-like cells (LLCs) derived from human induced pluripotent stem cells (hiPSCs). However, previous studies have encountered obstacles, such as limited cell longevity, insufficient testosterone production, and inefficiency of differentiation. To address these issues, we developed a novel protocol that includes forced NR5A1 expression, a cytokine cocktail promoting mesoderm differentiation, and a transitional shift from 3D to 2D cultures. The resultant cells survived on culture dishes for over 16 weeks, produced 22-fold more testosterone than the conventional method, and constituted a homogeneous population of LLCs with a differentiation efficiency exceeding 99% without purification. Furthermore, these LLCs were successfully engrafted subcutaneously into mice, resulting in increased serum testosterone levels. Our study will facilitate innovative therapeutic strategies for LOH syndrome.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102392"},"PeriodicalIF":5.9,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011921","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

A novel rapalog shows improved safety vs. efficacy in a human organoid model of polycystic kidney disease.

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-01-09 DOI: 10.1016/j.stemcr.2024.102395

Ramila E Gulieva, Parvaneh Ahmadvand, Benjamin S Freedman

引用次数: 0

From responsibility to responsibilization in stem cell research: An ethical framework. 干细胞研究从责任到责任：伦理框架。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-01-08 DOI: 10.1016/j.stemcr.2024.102389

Lars S Assen, Annelien L Bredenoord, Rosario Isasi, Morris A Fabbri, Marianna A Tryfonidou, Karin R Jongsma

引用次数: 0

Microvessel co-transplantation improves poor remuscularization by hiPSC-cardiomyocytes in a complex disease model of myocardial infarction and type 2 diabetes.

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-01-07 DOI: 10.1016/j.stemcr.2024.102394

Xuetao Sun, Jun Wu, Omar Mourad, Renke Li, Sara S Nunes

{"title":"Microvessel co-transplantation improves poor remuscularization by hiPSC-cardiomyocytes in a complex disease model of myocardial infarction and type 2 diabetes.","authors":"Xuetao Sun, Jun Wu, Omar Mourad, Renke Li, Sara S Nunes","doi":"10.1016/j.stemcr.2024.102394","DOIUrl":"https://doi.org/10.1016/j.stemcr.2024.102394","url":null,"abstract":"People with type 2 diabetes (T2D) are at a higher risk for myocardial infarction (MI) than age-matched healthy individuals. Here, we studied cell-based cardiac regeneration post MI in T2D rats modeling the co-morbid conditions in patients with MI. We recapitulated the T2D hallmarks and clinical aspects of diabetic cardiomyopathy using high-fat diet and streptozotocin in athymic rats, which were then subjected to MI and intramyocardial implantation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with or without rat adipose-derived microvessels (MVs). hiPSC-CM alone engrafted poorly. Co-delivery of hiPSC-CMs with MVs yielded a smaller infarct area and a thicker left ventricle wall. Additionally, MVs robustly integrated into the infarcted hearts, improved the survival of hiPSC-CMs, and improved cardiac function. MV-conditioned media also promoted hiPSC-CM maturation in vitro, increasing cardiomyocyte (CM) size in an interleukin (IL)-6-dependent manner. Given the availability of MVs from human adipose tissue, MVs present great translational potential for the treatment of heart failure in people with T2D.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102394"},"PeriodicalIF":5.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042257","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

Transplantation of genome-edited retinal organoids restores some fundamental physiological functions coordinated with severely degenerated host retinas. 基因组编辑的视网膜类器官移植恢复了与严重退化的宿主视网膜协调的一些基本生理功能。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-01-03 DOI: 10.1016/j.stemcr.2024.102393

Mikiya Watanabe, Takayuki Yamada, Chieko Koike, Masayo Takahashi, Masao Tachibana, Michiko Mandai

{"title":"Transplantation of genome-edited retinal organoids restores some fundamental physiological functions coordinated with severely degenerated host retinas.","authors":"Mikiya Watanabe, Takayuki Yamada, Chieko Koike, Masayo Takahashi, Masao Tachibana, Michiko Mandai","doi":"10.1016/j.stemcr.2024.102393","DOIUrl":"https://doi.org/10.1016/j.stemcr.2024.102393","url":null,"abstract":"We have previously shown that the transplantation of stem cell-derived retinal organoid (RO) sheets into animal models of end-stage retinal degeneration can lead to host-graft synaptic connectivity and restoration of vision, which was further improved using genome-edited Islet1-/- ROs (gROs) with a reduced number of ON-bipolar cells. However, the details of visual function restoration using this regenerative therapeutic approach have not yet been characterized. Here, we evaluated the electrophysiological properties of end-stage rd1 retinas after transplantation (TP-rd1) and compared them with those of wild-type (WT) retinas using multi-electrode arrays. Notably, retinal ganglion cells (RGCs) in TP-rd1 retinas acquired light sensitivity comparable to that of WT retinas. Furthermore, RGCs in TP-rd1 retinas showed light adaptation to a photopic background and responded to flickering stimuli. These results demonstrate that transplantation of gRO sheets may restore some fundamental physiological functions, possibly coordinating with the remaining functions in retinas with end-stage degeneration.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102393"},"PeriodicalIF":5.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011922","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