骨形态发生蛋白 4 可诱导小鼠造血内皮细胞的造血干细胞发育。

IF 5.9 2区 医学 Q1 CELL & TISSUE ENGINEERING
Stem Cell Reports Pub Date : 2024-12-10 Epub Date: 2024-11-14 DOI:10.1016/j.stemcr.2024.10.005
Mariko Tsuruda, Saori Morino-Koga, Xueyu Zhao, Shingo Usuki, Kei-Ichiro Yasunaga, Tomomasa Yokomizo, Ryuichi Nishinakamura, Toshio Suda, Minetaro Ogawa
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引用次数: 0

摘要

造血干细胞(HSCs)是在小鼠胚胎发育过程中由造血内皮细胞(HECs)发育而来的。了解造血干细胞发育所需的信号分子对体外衍生造血干细胞至关重要。我们以前曾在无血清培养条件下,用干细胞因子、血小板生成素和内皮馈源层从胚胎10.5天(E10.5)分离的胚胎HECs中诱导出造血干细胞。在此,我们旨在阐明从早期HECs诱导造血干细胞的信号要求。单细胞 RNA 测序(RNA-seq)分析检测到 E9.5 HECs 中的骨形态发生蛋白(BMP)信号激活。在培养条件中加入BMP4可从E9.5 HECs中诱导出造血干细胞。此外,从E9.5胚胎中分离出表达BMP4受体的HECs还能富集具有造血干细胞形成能力的祖细胞。这项研究确定了 BMP4 是促进早期 HECs 向 HSCs 分化的重要因子,为体外衍生 HSCs 开辟了新的可能性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Bone morphogenetic protein 4 induces hematopoietic stem cell development from murine hemogenic endothelial cells in culture.

Hematopoietic stem cells (HSCs) develop from hemogenic endothelial cells (HECs) during mouse embryogenesis. Understanding the signaling molecules required for HSC development is crucial for the in vitro derivation of HSCs. We previously induced HSCs from embryonic HECs, isolated at embryonic day 10.5 (E10.5), in serum-free culture conditions with stem cell factor, thrombopoietin, and an endothelial feeder layer. Here, we aimed to elucidate signal requirements for inducing HSCs from earlier-stage HECs. Single-cell RNA sequencing (RNA-seq) analysis detected bone morphogenetic protein (BMP) signaling activation in E9.5 HECs. Adding BMP4 to the culture conditions led to the induction of HSCs from E9.5 HECs. Furthermore, isolating BMP4 receptor-expressing HECs from E9.5 embryos enriched progenitors with HSC-forming ability. This study identified BMP4 as an essential factor promoting the differentiation of early HECs into HSCs, opening up new possibilities for the in vitro derivation of HSCs.

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来源期刊
Stem Cell Reports
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.
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