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人类输尿管芽类器官再现分支形态发生及分化为功能性集尿管细胞类型
作者:小柯机器人 发布时间:2022/8/31 15:16:04

美国哈佛医学院Joseph V. Bonventre和Kyle W. McCracken共同合作近期取得重要工作进展,他们成功利用人类输尿管芽类器官再现了分支形态发生及分化为功能性集尿管细胞类型。该项研究成果2022年8月29日在线发表于《自然—生物技术》上。

研究人员将hPSCs利用高效且无血清的方法分化为输尿管芽(UB)类器官和功能性CD细胞。hPSCs首先以90%的效率被诱导成前肾祖细胞,然后聚集成具有类似于肾管分子特征的球体。在三维基质中,球体形成UB类器官,表现出类似于胎儿UB的分支形态,并纠正了RET表达的远端尖端定位。类器官来源的细胞在嵌合胎肾外植体培养中融入到祖细胞生态位的UB尖端。

在后期,UB类器官分化为CD类器官,单细胞RNA测序估计其中包含>95%的CD细胞类型。CD上皮细胞表现出肾电生理功能,主细胞具有ENaC介导的矢量钠转运活性和FOXI1诱导的闰细胞的V型ATP酶质子泵活性。

据介绍,将人类多能干细胞(hPSCs)定向分化为功能性输尿管和集合管(CD)上皮细胞对于肾脏再生医学至关重要。

附:英文原文

Title: Human ureteric bud organoids recapitulate branching morphogenesis and differentiate into functional collecting duct cell types

Author: Shi, Min, McCracken, Kyle W., Patel, Ankit B., Zhang, Weitao, Ester, Lioba, Valerius, M. Todd, Bonventre, Joseph V.

Issue&Volume: 2022-08-29

Abstract: Directed differentiation of human pluripotent stem cells (hPSCs) into functional ureteric and collecting duct (CD) epithelia is essential to kidney regenerative medicine. Here we describe highly efficient, serum-free differentiation of hPSCs into ureteric bud (UB) organoids and functional CD cells. The hPSCs are first induced into pronephric progenitor cells at 90% efficiency and then aggregated into spheres with a molecular signature similar to the nephric duct. In a three-dimensional matrix, the spheres form UB organoids that exhibit branching morphogenesis similar to the fetal UB and correct distal tip localization of RET expression. Organoid-derived cells incorporate into the UB tips of the progenitor niche in chimeric fetal kidney explant culture. At later stages, the UB organoids differentiate into CD organoids, which contain >95% CD cell types as estimated by single-cell RNA sequencing. The CD epithelia demonstrate renal electrophysiologic functions, with ENaC-mediated vectorial sodium transport by principal cells and V-type ATPase proton pump activity by FOXI1-induced intercalated cells.

DOI: 10.1038/s41587-022-01429-5

Source: https://www.nature.com/articles/s41587-022-01429-5

期刊信息

Nature Biotechnology:《自然—生物技术》,创刊于1996年。隶属于施普林格·自然出版集团,最新IF:31.864
官方网址:https://www.nature.com/nbt/
投稿链接:https://mts-nbt.nature.com/cgi-bin/main.plex