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18.08.18 Resolving the cellular basis of mouse pancreas development

last modified Aug 09, 2018 10:37 AM
The Simons and Huch labs, with Cambridge Stem Cell Institute colleagues, tease out the cellular mechanisms by which the pancreas develops its branched ductal structures
18.08.18 Resolving the cellular basis of mouse pancreas development

Clones of labelled stem cells in developing mouse pancreas

Defining Lineage Potential and Fate Behavior of Precursors during Pancreas Development

Sznurkowska MK et al. (2018) Dev Cell Jul 18. pii: S1534-5807(18)30553-7. DOI: 10.1016/j.devcel.2018.06.028. [Epub ahead of print]

Abstract from the paper

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.

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Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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