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

Mirza Muhammad Fahd Qadir, Silvia Álvarez-Cubela, Dagmar Klein, Giacomo Lanzoni, Carlos García-Santana, Abelardo Montalvo, Fabiola Pláceres-Uray, Emilia Maria Cristina Mazza, Camillo Ricordi, Luca Alessandro Inverardi, Ricardo Luis Pastori, Juan Domínguez-Bendala

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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 + /ALK3 bright+ 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 + /ALK3 bright+ 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. Qadir et al. describe and characterize a population of multipotent, BMP-7-responsive progenitor-like cells within the human exocrine pancreas. These cells are characterized by the expression of PDX1 and ALK3, a canonical BMP receptor. Their findings shed new light on potential regenerative pathways in the human pancreas.

Original languageEnglish (US)
Pages (from-to)2408-2420
Number of pages13
JournalCell Reports
Volume22
Issue number9
DOIs
StatePublished - Feb 27 2018

Keywords

  • ALK3
  • PDX1
  • beta cell regeneration
  • human pancreatic progenitor cells
  • islet regeneration

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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