APA
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Qadir, F., Álvarez-Cubela, S., Klein, D., van Dijk, J., Muñiz-Anquela, R., Moreno-Hernández, Y. B., … Domínguez-Bendala, J. (2020). Single-cell resolution analysis of the human pancreatic ductal progenitor cell niche. Proceedings of the National Academy of Sciences.
Chicago/Turabian
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Qadir, Fahd, Silvia Álvarez-Cubela, D. Klein, Jasmijn van Dijk, Rocío Muñiz-Anquela, Yaisa B Moreno-Hernández, G. Lanzoni, et al. “Single-Cell Resolution Analysis of the Human Pancreatic Ductal Progenitor Cell Niche.” Proceedings of the National Academy of Sciences (2020).
MLA
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Qadir, Fahd, et al. “Single-Cell Resolution Analysis of the Human Pancreatic Ductal Progenitor Cell Niche.” Proceedings of the National Academy of Sciences, 2020.
BibTeX Click to copy
@article{fahd2020a,
title = {Single-cell resolution analysis of the human pancreatic ductal progenitor cell niche},
year = {2020},
journal = {Proceedings of the National Academy of Sciences},
author = {Qadir, Fahd and Álvarez-Cubela, Silvia and Klein, D. and van Dijk, Jasmijn and Muñiz-Anquela, Rocío and Moreno-Hernández, Yaisa B and Lanzoni, G. and Sadiq, Saad and Navarro-Rubio, Belén and Garcia, Michael T. and Díaz, Á. and Johnson, Kevin and Sant, David W and Ricordi, C. and Griswold, A. and Pastori, R. and Domínguez-Bendala, J.}
}
Significance The existence of progenitors within pancreatic ducts has been studied for decades, but the hypothesis that they may help regenerate the adult endocrine compartment (chiefly insulin-producing β-cells) remains contentious. Here, we examine the single-cell transcriptome of the human ductal tree. Our data confirm the paradigm-shifting notion that specific lineages, long thought to be cast in stone, are in fact in a state of flux between differentiation stages. In addition to pro-ductal and pro-acinar transcriptomic gradients, our analysis suggests the existence of a third (ducto-endocrine) differentiation axis. Such prediction was experimentally validated by transplanting sorted progenitor-like cells, which revealed their tri-lineage differentiation potential. Our findings further indicate that progenitors might be activated in situ for therapeutic purposes. We have described multipotent progenitor-like cells within the major pancreatic ducts (MPDs) of the human pancreas. They express PDX1, its surrogate surface marker P2RY1, and the bone morphogenetic protein (BMP) receptor 1A (BMPR1A)/activin-like kinase 3 (ALK3), but not carbonic anhydrase II (CAII). Here we report the single-cell RNA sequencing (scRNA-seq) of ALK3bright+-sorted ductal cells, a fraction that harbors BMP-responsive progenitor-like cells. Our analysis unveiled the existence of multiple subpopulations along two major axes, one that encompasses a gradient of ductal cell differentiation stages, and another featuring cells with transitional phenotypes toward acinar tissue. A third potential ducto-endocrine axis is revealed upon integration of the ALK3bright+ dataset with a single-cell whole-pancreas transcriptome. When transplanted into immunodeficient mice, P2RY1+/ALK3bright+ populations (enriched in PDX1+/ALK3+/CAII− cells) differentiate into all pancreatic lineages, including functional β-cells. This process is accelerated when hosts are treated systemically with an ALK3 agonist. We found PDX1+/ALK3+/CAII− progenitor-like cells in the MPDs of types 1 and 2 diabetes donors, regardless of the duration of the disease. Our findings open the door to the pharmacological activation of progenitor cells in situ.
