SFRP4(+) stromal cell subpopulation with IGF1 signaling in human endometrial regeneration.

SFRP4(+) stromal cell subpopulation with IGF1 signaling in human endometrial regeneration.
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人类子宫内膜再生中具有 IGF1 信号传导的 SFRP4 基质细胞亚群

DOI:
10.1038/s41421-022-00438-7
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发表时间:
2022-09-27
期刊:
影响因子:
33.5
通讯作者:
Zou, XiaoHui
Zou, XiaoHui
中科院分区:
生物学1区
文献类型:
--
作者:
Wu, Bingbing;Li, Yu;Nie, Nanfang;Shen, Xilin;Jiang, Wei;Liu, Yanshan;Gong, Lin;An, Chengrui;Zhao, Kun;Yao, Xudong;Yuan, Chunhui;Hu, Jinghui;Zhao, Wei;Qian, Jianhua;Zou, XiaoHui

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我们对损伤后全层子宫内膜再生的理解受到负责器官功能的细胞群的不完整分子表征的限制。为了帮助填补这一知识空白,我们使用无偏倚的单细胞RNA测序对来自两个月经期(增殖期和分泌期)的10,551个全层正常人子宫细胞进行了表征。我们解剖了全层子宫组织的主要细胞类型(上皮细胞、间质细胞、内皮细胞和免疫细胞)的细胞异质性,人类子宫细胞在整个月经周期的细胞群体结构。我们鉴定了一个SFRP 4+基质细胞亚群,该亚群在月经周期的人子宫内膜再生阶段高度富集,SFRP 4+基质细胞在体外可显著促进人子宫内膜上皮类器官的增殖,在体内可通过IGF 1信号通路促进子宫内膜上皮腺体再生和子宫内膜全层损伤。我们的全层子宫组织细胞图谱揭示了人类子宫内膜每月再生过程中的细胞异质性,细胞群结构及其细胞间通讯,这为人类子宫内膜再生的生物学以及针对子宫内膜损伤和子宫内膜粘连的再生医学治疗的发展提供了见解。
Our understanding of full-thickness endometrial regeneration after injury is limited by an incomplete molecular characterization of the cell populations responsible for the organ functions. To help fill this knowledge gap, we characterized 10,551 cells of full-thickness normal human uterine from two menstrual phases (proliferative and secretory phase) using unbiased single cell RNA-sequencing. We dissected cell heterogeneity of main cell types (epithelial, stromal, endothelial, and immune cells) of the full thickness uterine tissues, cell population architectures of human uterus cells across the menstrual cycle. We identified an SFRP4+ stromal cell subpopulation that was highly enriched in the regenerative stage of the human endometria during the menstrual cycle, and the SFRP4+ stromal cells could significantly enhance the proliferation of human endometrial epithelial organoid in vitro, and promote the regeneration of endometrial epithelial glands and full-thickness endometrial injury through IGF1 signaling pathway in vivo. Our cell atlas of full-thickness uterine tissues revealed the cellular heterogeneities, cell population architectures, and their cell–cell communications during the monthly regeneration of the human endometria, which provide insight into the biology of human endometrial regeneration and the development of regenerative medicine treatments against endometrial damage and intrauterine adhesion.
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