Defining Lineage Potential and Fate Behavior of Precursors during Pancreas Development.
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Authors
Sznurkowska, Magdalena
Shaw, Sonia
Hindley, Christopher J
Gottgens, Berthold
Publication Date
2018-08Journal Title
Developmental cell
ISSN
1534-5807
Publisher
Elsevier
Volume
46
Issue
3
Pages
360-375.e5
Language
eng
Type
Article
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Sznurkowska, M., Hannezo, E., Azzarelli, R., Rulands, S., Shaw, S., Hindley, C. J., Nichols, J., et al. (2018). Defining Lineage Potential and Fate Behavior of Precursors during Pancreas Development.. Developmental cell, 46 (3), 360-375.e5. https://doi.org/10.1016/j.devcel.2018.06.028
Abstract
Pancreas development involves a coordinated process in which an early phase of cell segregation is proceeded by a longer phase of lineage restriction, expansion and tissue remodeling. By combining clonal tracing and whole-mount reconstruction with proliferation kinetics and single-cell transcriptional profiling, we define the functional basis of pancreas morphogenesis. We show that the large-scale organization of mouse pancreas can be traced to the activity of self-renewing precursors positioned at the termini of growing ducts, which act collectively to drive serial rounds of stochastic ductal bifurcation balanced by termination. During this phase of branching morphogenesis, multipotent precursors become progressively fate restricted, giving rise to self-renewing acinar-committed precursors that are conveyed with growing ducts, as well as ductal progenitors that expand the trailing ducts and give rise to delaminating endocrine cells. These findings define quantitatively how the functional behavior and lineage progression of precursor pools determine the large-scale patterning of pancreatic sub-compartments.
Keywords
Pancreas, Stem Cells, Animals, Cell Differentiation, Cell Proliferation, Gene Expression Regulation, Developmental, Cell Lineage, Morphogenesis, Organogenesis, Endocrine Cells, Acinar Cells
Sponsorship
Wellcome Trust
Funder references
WELLCOME TRUST (098357/Z/12/Z)
MRC (1514251)
MRC (MR/K018329/1)
Wellcome Trust (097922/Z/11/Z)
MRC (MC_PC_12009)
WELLCOME TRUST (110326/Z/15/Z)
WELLCOME TRUST (104151/Z/14/Z)
MEDICAL RESEARCH COUNCIL (MR/M008975/1)
Identifiers
External DOI: https://doi.org/10.1016/j.devcel.2018.06.028
This record's URL: https://www.repository.cam.ac.uk/handle/1810/280514