生物
类有机物
祖细胞
人口
肠内分泌细胞
移植
胰腺
细胞生物学
小岛
间充质干细胞
细胞分化
干细胞
免疫学
内科学
内分泌系统
内分泌学
胰岛素
遗传学
基因
激素
社会学
人口学
医学
作者
Daisong Wang,Jingqiang Wang,Lanyue Bai,Hong Pan,Feng Huang,Hans Clevers,Yi Arial Zeng
出处
期刊:Cell
[Elsevier]
日期:2020-03-01
卷期号:180 (6): 1198-1211.e19
被引量:108
标识
DOI:10.1016/j.cell.2020.02.048
摘要
It has generally proven challenging to produce functional β cells in vitro. Here, we describe a previously unidentified protein C receptor positive (Procr+) cell population in adult mouse pancreas through single-cell RNA sequencing (scRNA-seq). The cells reside in islets, do not express differentiation markers, and feature epithelial-to-mesenchymal transition characteristics. By genetic lineage tracing, Procr+ islet cells undergo clonal expansion and generate all four endocrine cell types during adult homeostasis. Sorted Procr+ cells, representing ∼1% of islet cells, can robustly form islet-like organoids when cultured at clonal density. Exponential expansion can be maintained over long periods by serial passaging, while differentiation can be induced at any time point in culture. β cells dominate in differentiated islet organoids, while α, δ, and PP cells occur at lower frequencies. The organoids are glucose-responsive and insulin-secreting. Upon transplantation in diabetic mice, these organoids reverse disease. These findings demonstrate that the adult mouse pancreatic islet contains a population of Procr+ endocrine progenitors.
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