Bi-potential hPSCs-derived Müllerian Duct-like Cells for Full-thickness and Functional Endometrium Regeneration
Bi-potential hPSCs-derived Müllerian Duct-like Cells for Full-thickness and Functional Endometrium Regeneration
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用于全层和功能性子宫内膜再生的双能 hPSC 来源的穆氏管样细胞
DOI：
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发表时间：
2022
影响因子：
7.2
通讯作者：
XiaoHui Zou
中科院分区：
文献类型：
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作者：
Lin Gong;Nanfang Nie;Xilin Shen;Jingwei Zhang;Yu Li;Yixiao Liu;Jiaqi Xu;Wei Jiang;Yanshan Liu;Hua Liu;Bingbing Wu;XiaoHui Zou
基于干细胞的组织再生策略是治疗严重子宫内膜损伤的有前景的治疗方法。然而，几乎没有合适的种子细胞来再生主要由上皮和间质组成的全层子宫内膜。女性胚胎发育中的苗勒管发育为子宫内膜上皮和间质。因此，我们首先使用一种明确和有效的方案来培养人多能干细胞(HPSC)来源的苗勒管样细胞(MDLC)。MDLCs具有双潜能，可在体外和体内逐渐分化为子宫内膜上皮细胞和间质细胞，并重建全层子宫内膜。此外，MDLCs在全层子宫内膜损伤大鼠体内具有重建子宫内膜结构和恢复妊娠功能的原位修复能力，并通过单细胞RNA测序(scRNA-seq)揭示其分化命运。我们的研究为hPSC分化为子宫内膜提供了一种策略，并为损伤的子宫内膜再生提供了一种替代种子细胞。
Stem cell-based tissue regeneration strategies are promising treatments for severe endometrial injuries. However, there are few appropriate seed cells for regenerating a full-thickness endometrium, which mainly consists of epithelia and stroma. Müllerian ducts in female embryonic development develop into endometrial epithelia and stroma. Hence, we first generated human pluripotent stem cells (hPSC)-derived Müllerian duct-like cells (MDLCs) using a defined and effective protocol. The MDLCs are bi-potent, can gradually differentiate into endometrial epithelial and stromal cells, and reconstitute full-thickness endometrium in vitro and in vivo. Furthermore, MDLCs showed the in situ repair capabilities of reconstructing endometrial structure and recovering pregnancy function in full-thickness endometrial injury rats, and their differentiation fate was revealed by single-cell RNA sequencing (scRNA-seq). Our study provides a strategy for hPSC differentiation into endometrial lineages and an alternative seed cell for injured endometrial regeneration.