Developmental regulation of endothelial-to-hematopoietic transition from induced pluripotent stem cells.

IF 5.1 2区医学 Q1 CELL & TISSUE ENGINEERING

Stem Cell Reports Pub Date : 2025-09-18 DOI:10.1016/j.stemcr.2025.102641

Rachel Wellington, Xiaoyi Cheng, Shuvra Dutta, Clyde A Campbell, Cole Trapnell, Raquel Espin-Palazon, Brandon Hadland, Sergei Doulatov

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引用次数: 0

Abstract

Hematopoietic stem cells (HSCs) arise in embryogenesis from a specialized hemogenic endothelium (HE) via endothelial-to-hematopoietic transition (EHT). While induced pluripotent stem cells (iPSCs) give rise to HE with robust hemogenic potential, bona fide HSC generation from iPSCs remains challenging. We map single-cell dynamics of EHT from iPSCs and integrate it with human embryo datasets to identify ligand-receptor interactions that drive transcriptional divergence between iPSC-derived and embryonic cell states. The expression of endothelial genes predicted to be regulated by FGF signaling was incompletely repressed during iPSC-derived EHT. FGF activity declined at the onset of EHT to enable normal hematopoiesis in the zebrafish, and chemical inhibition of FGF signaling during EHT enhanced HSC and progenitor generation in the zebrafish and from iPSCs. In summary, we generate a single-cell map of iPSC-derived EHT, identify ligand-receptor interactions that can improve iPSC differentiation, and uncover elevated FGF signaling as a barrier to hematopoiesis.

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诱导多能干细胞内皮向造血转化的发育调控。

造血干细胞（hsc）是在胚胎发生过程中由特化的造血内皮（HE）通过内皮-造血转化（EHT）产生的。虽然诱导多能干细胞（iPSCs）产生具有强大造血潜能的HE，但从iPSCs生成真正的HSC仍然具有挑战性。我们绘制了来自ipsc的EHT单细胞动力学图谱，并将其与人类胚胎数据集相结合，以确定驱动ipsc衍生细胞和胚胎细胞状态之间转录差异的配体-受体相互作用。在ipsc衍生的EHT中，被预测受FGF信号调节的内皮基因的表达不完全被抑制。在EHT开始时，FGF活性下降，使斑马鱼能够正常造血，并且EHT期间FGF信号的化学抑制增强了斑马鱼和iPSCs中HSC和祖细胞的生成。总之，我们生成了iPSC衍生的EHT的单细胞图谱，确定了可以改善iPSC分化的配体-受体相互作用，并揭示了FGF信号升高作为造血障碍的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY

CiteScore

10.50

自引率

1.70%

发文量

200

审稿时长

28 weeks

期刊介绍： Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.