Wnt Signaling Separates the Progenitor and Endocrine Compartments during Pancreas Development
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1-s2.0-S2211124719305637-main.pdf
Description
Published version
Size
4.05 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Sharon, Nadav
Vanderhooft, Jordan
Straubhaar, Juerg
Mueller, Jonas Weylin
Chawla, Raghav
Zhou, Quan
Engquist, Elise N.
Trapnell, Cole
Gifford, David K
Melton, Douglas A.
Date Issued
May 2019
Journal
Cell Reports
Publisher
Elsevier BV
Citation
Sharon, Nadav et al. "Wnt Signaling Separates the Progenitor and Endocrine Compartments during Pancreas Development." Cell Reports 27, 8 (May 2019): P2281-2291.e5 © 2019 The Authors
Version
Final published version
Abstract
In vitro differentiation of pluripotent cells into β cells is a promising alternative to cadaveric-islet transplantation as a cure for type 1 diabetes (T1D). During the directed differentiation of human embryonic stem cells (hESCS) by exogenous factors, numerous genes that affect the differentiation process are turned on and off autonomously. Manipulating these reactions could increase the efficiency of differentiation and provide a more complete control over the final composition of cell populations. To uncover in vitro autonomous responses, we performed single-cell RNA sequencing on hESCs as they differentiate in spherical clusters. We observed that endocrine cells and their progenitors exist beside one another in separate compartments that activate distinct genetic pathways. WNT pathway inhibition in the endocrine domain of the differentiating clusters reveals a necessary role for the WNT inhibitor APC during islet formation in vivo. Accordingly, WNT inhibition in vitro causes an increase in the proportion of differentiated endocrine cells.
MIT Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2019.04.083
