Cell stem cell最新文献

Integrating collecting systems in human kidney organoids through fusion of distal nephron to ureteric bud 通过远端肾元与输尿管芽融合整合人肾类器官收集系统

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-05-08 DOI: 10.1016/j.stem.2025.04.008

Min Shi, Brittney Crouse, Nambirajan Sundaram, Naomi Pode Shakked, Konrad Thorner, Nathaniel M. King, Parna Dutta, Lioba Ester, Weitao Zhang, Vinothini Govindarajah, Raphael Kopan, Cristina Cebrian, Christopher N. Mayhew, Michael A. Helmrath, Joseph V. Bonventre, Kyle W. McCracken

{"title":"Integrating collecting systems in human kidney organoids through fusion of distal nephron to ureteric bud","authors":"Min Shi, Brittney Crouse, Nambirajan Sundaram, Naomi Pode Shakked, Konrad Thorner, Nathaniel M. King, Parna Dutta, Lioba Ester, Weitao Zhang, Vinothini Govindarajah, Raphael Kopan, Cristina Cebrian, Christopher N. Mayhew, Michael A. Helmrath, Joseph V. Bonventre, Kyle W. McCracken","doi":"10.1016/j.stem.2025.04.008","DOIUrl":"https://doi.org/10.1016/j.stem.2025.04.008","url":null,"abstract":"Kidneys maintain homeostasis through an array of parallel nephrons, which fuse during development to a system of collecting ducts (CDs), establishing the essential luminal pathway for excretion of metabolic waste. Human kidney organoids derived from pluripotent stem cells (human pluripotent stem cells [hPSCs]) generate nephrons that lack CDs and terminate as blind-ended tubules, limiting their functional potential. Here, we describe a developmentally inspired hPSC differentiation system that addresses this deficiency through assembly of induced nephrogenic mesenchyme with ureteric bud (UB) progenitors, leading to a CD network functionally integrated in kidney organoids through fusion with the distal tubule. The nephron fusion occurs stereotypically and is regulated by proximal-distal nephron patterning, which can be modulated through temporal manipulation of developmental pathways. This work provides a platform for interrogating the principles and mechanisms underlying nephron-UB fusion and a framework for engineering unobstructed nephrons with collecting systems, an important step toward <em>de novo</em> generation of functional kidney tissue.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"187 6 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

3D reconstruction of a human Carnegie stage 9 embryo provides a snapshot of early body plan formation 人类卡内基9期胚胎的三维重建提供了早期身体计划形成的快照

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-05-08 DOI: 10.1016/j.stem.2025.04.007

Yang Yuan, Xiaoyan Wang, Xiaodi Yan, Nannan He, Xiaojian Lu, Jingyu Yang, Xinwei Xie, Huiyao Yuan, Naixin Chen, Yinbo Liu, Hongan Ren, Runzhao Zhang, Lina Cui, Pengcheng Ren, Sirui Lin, Shuhan Cheng, Xiaolong Yang, Yifei Guo, Rong Li, Tianyi Yan, Leqian Yu

{"title":"3D reconstruction of a human Carnegie stage 9 embryo provides a snapshot of early body plan formation","authors":"Yang Yuan, Xiaoyan Wang, Xiaodi Yan, Nannan He, Xiaojian Lu, Jingyu Yang, Xinwei Xie, Huiyao Yuan, Naixin Chen, Yinbo Liu, Hongan Ren, Runzhao Zhang, Lina Cui, Pengcheng Ren, Sirui Lin, Shuhan Cheng, Xiaolong Yang, Yifei Guo, Rong Li, Tianyi Yan, Leqian Yu","doi":"10.1016/j.stem.2025.04.007","DOIUrl":"https://doi.org/10.1016/j.stem.2025.04.007","url":null,"abstract":"The Carnegie stage 9 (CS9) embryo is a pivotal phase signifying the conclusion of gastrulation and the onset of early organogenesis, crucial for initiating major organ system development. Utilizing spatial transcriptomics, we analyzed an intact CS9 human embryo in a spatially detailed manner. Through the examination of 75 transverse cryosections, we digitally reconstructed a 3D model, allowing us to identify diverse cell types, including those from brain and spine regions, the primitive gut tube, distinct somite formation stages, somatic mesoderm, splanchnic mesoderm, etc. Notably, we observed two distinct trajectories of hindbrain development, pinpointed the isthmic organizer at the midbrain-hindbrain boundary, delineated the bi-layered structure of neuromesodermal progenitor (NMP) cells, and described the early aorta formation and primordial germ cells (PGCs) presence in the aorta-gonad-mesonephros (AGM) region. This study provides key insights into the transcriptomic and spatial intricacies shaping the human body plan.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"35 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Specification of human brain regions with orthogonal gradients of WNT and SHH in organoids reveals patterning variations across cell lines 用类器官中WNT和SHH的正交梯度对人类大脑区域的描述揭示了不同细胞系间的模式变化

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-05-01 DOI: 10.1016/j.stem.2025.04.006

Soraya Scuderi, Tae-Yun Kang, Alexandre Jourdon, Alex Nelson, Liang Yang, Feinan Wu, George M. Anderson, Jessica Mariani, Livia Tomasini, Vivekananda Sarangi, Alexej Abyzov, Andre Levchenko, Flora M. Vaccarino

{"title":"Specification of human brain regions with orthogonal gradients of WNT and SHH in organoids reveals patterning variations across cell lines","authors":"Soraya Scuderi, Tae-Yun Kang, Alexandre Jourdon, Alex Nelson, Liang Yang, Feinan Wu, George M. Anderson, Jessica Mariani, Livia Tomasini, Vivekananda Sarangi, Alexej Abyzov, Andre Levchenko, Flora M. Vaccarino","doi":"10.1016/j.stem.2025.04.006","DOIUrl":"https://doi.org/10.1016/j.stem.2025.04.006","url":null,"abstract":"The repertoire of neurons and their progenitors depends on their location along the antero-posterior and dorso-ventral axes of the neural tube. To model these axes, we designed the Dual Orthogonal-Morphogen Assisted Patterning System (Duo-MAPS) diffusion device to expose spheres of induced pluripotent stem cells (iPSCs) to concomitant orthogonal gradients of a posteriorizing and a ventralizing morphogen, activating WNT and SHH signaling, respectively. Comparison with single-cell transcriptomes from the fetal human brain revealed that Duo-MAPS-patterned organoids generated an extensive diversity of neuronal lineages from the forebrain, midbrain, and hindbrain. WNT and SHH crosstalk translated into early patterns of gene expression programs associated with the generation of specific brain lineages with distinct functional networks. Human iPSC lines showed substantial interindividual and line-to-line variations in their response to morphogens, highlighting that genetic and epigenetic variations may influence regional specification. Morphogen gradients promise to be a key approach to model the brain in its entirety.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"24 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Shaping intestinal organoids: Engineering crypt curvature to guide stem cell niches 塑造肠道类器官：工程隐窝曲率引导干细胞壁龛

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-05-01 DOI: 10.1016/j.stem.2025.03.015

Riccardo Barrile, Magdalena Kasendra

引用次数: 0

Dopaminergic neurons entering the brain under the immunological cover of darkness 多巴胺能神经元在黑暗的免疫掩护下进入大脑

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-05-01 DOI: 10.1016/j.stem.2025.04.004

Timothy Chai, Julie Y. Chen, Kyle M. Loh

引用次数: 0

Bioengineering innovations for neural organoids with enhanced fidelity and function 增强保真度和功能的类神经器官生物工程创新