P2RY1/ALK3-Expressing Cells within the Adult Human Exocrine Pancreas Are BMP-7 Expandable and Exhibit Progenitor-like Characteristics

Cell Reports
Mirza Muhammad Fahd QadirJuan Domínguez-Bendala

Abstract

Treatment of human pancreatic non-endocrine tissue with Bone Morphogenetic Protein 7 (BMP-7) leads to the formation of glucose-responsive β-like cells. Here, we show that BMP-7 acts on extrainsular cells expressing PDX1 and the BMP receptor activin-like kinase 3 (ALK3/BMPR1A). In vitro lineage tracing indicates that ALK3+ cell populations are multipotent. PDX1+/ALK3+ cells are absent from islets but prominently represented in the major pancreatic ducts and pancreatic duct glands. We identified the purinergic receptor P2Y1 (P2RY1) as a surrogate surface marker for PDX1. Sorted P2RY1+/ALK3bright+ cells form BMP-7-expandable colonies characterized by NKX6.1 and PDX1 expression. Unlike the negative fraction controls, these colonies can be differentiated into multiple pancreatic lineages upon BMP-7 withdrawal. RNA-seq further corroborates the progenitor-like nature of P2RY1+/ALK3bright+ cells and their multilineage differentiation potential. Our studies confirm the existence of progenitor cells in the adult human pancreas and suggest a specific anatomical location within the ductal and glandular networks.

Citations

Jan 26, 2020·Cells·Bushra Memon, Essam M Abdelalim
Nov 22, 2019·The Journal of Clinical Endocrinology and Metabolism·Michael G WhiteJames A M Shaw
Aug 29, 2020·Diabetes/metabolism Research and Reviews·Bushra MemonEssam M Abdelalim
Apr 2, 2020·Frontiers in Pharmacology·Mahmoud G KhalafallaGary A Weisman
Jul 1, 2020·Nature Communications·Mirza Muhammad Fahd QadirJuan Domínguez-Bendala
May 2, 2020·Proceedings of the National Academy of Sciences of the United States of America·Mirza Muhammad Fahd QadirJuan Domínguez-Bendala
Nov 26, 2020·International Journal of Molecular Sciences·Ivana NovakGanga Deshar
Mar 23, 2021·Protein & Cell·Xiaofei ZhangTao Xu
May 20, 2021·Trends in Endocrinology and Metabolism : TEM·Juan Domínguez-BendalaRicardo Luis Pastori
Sep 28, 2021·Frontiers in Endocrinology·Hyo Jeong YongYue J Wang

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Datasets Mentioned

BETA
E-MTAB-463

Methods Mentioned

BETA
RNA-seq
Flow Cytometry

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