Defining Lineage Potential and Fate Behavior of Precursors during Pancreas Development.
View / Open Files
Authors
Sznurkowska, Magdalena K
Hannezo, Edouard
Azzarelli, Roberta
Nestorowa, Sonia
Hindley, Christopher J
Göttgens, Berthold
Huch, Meritxell
Simons, Benjamin D
Publication Date
2018-08-06Journal Title
Dev Cell
ISSN
1534-5807
Publisher
Elsevier BV
Volume
46
Issue
3
Pages
360-375.e5
Language
eng
Type
Article
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Sznurkowska, M. K., Hannezo, E., Azzarelli, R., Rulands, S., Nestorowa, S., Hindley, C. J., Nichols, J., et al. (2018). Defining Lineage Potential and Fate Behavior of Precursors during Pancreas Development.. Dev 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 followed 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
acini, branching morphogenesis, development, differentiation, ducts, islets, pancreas, specification, tubulogenesis, Acinar Cells, Animals, Cell Differentiation, Cell Lineage, Cell Proliferation, Endocrine Cells, Gene Expression Regulation, Developmental, Morphogenesis, Organogenesis, Pancreas, Stem Cells
Sponsorship
Wellcome Trust
Funder references
Wellcome Trust (098357/Z/12/Z)
MRC (1514251)
Medical Research Council (MR/K018329/1)
Wellcome Trust (097922/Z/11/Z)
Medical Research Council (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
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.
Recommended or similar items
The current recommendation prototype on the Apollo Repository will be turned off on 03 February 2023. Although the pilot has been fruitful for both parties, the service provider IKVA is focusing on horizon scanning products and so the recommender service can no longer be supported. We recognise the importance of recommender services in supporting research discovery and are evaluating offerings from other service providers. If you would like to offer feedback on this decision please contact us on: support@repository.cam.ac.uk