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However, there are few appropriate seed cells for regenerating a full-thickness endometrium, which mainly consists of epithelia and stroma. M\u00fcllerian ducts in female embryonic development develop into endometrial epithelia and stroma. Hence, we first generated human pluripotent stem cells (hPSC)-derived M\u00fcllerian 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.<\/jats:p>","DOI":"10.1038\/s41536-022-00263-2","type":"journal-article","created":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T10:17:34Z","timestamp":1669198654000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Bi-potential hPSC-derived M\u00fcllerian duct-like cells for full-thickness and functional endometrium regeneration"],"prefix":"10.1038","volume":"7","author":[{"given":"Lin","family":"Gong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanfang","family":"Nie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8746-5801","authenticated-orcid":false,"given":"Xilin","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixiao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6685-7053","authenticated-orcid":false,"given":"Wei","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanshan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingbing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9563-0301","authenticated-orcid":false,"given":"XiaoHui","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,23]]},"reference":[{"key":"263_CR1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1095\/biolreprod65.5.1311","volume":"65","author":"CA Gray","year":"2001","unstructured":"Gray, C. 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