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Tracing the cellular dynamics of sebaceous gland development in normal and perturbed states.

Accepted version
Peer-reviewed

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Authors

Andersen, Marianne Stemann  ORCID logo  https://orcid.org/0000-0001-6751-5453
Ulyanchenko, Svetlana  ORCID logo  https://orcid.org/0000-0003-3124-9178
Antoku, Yasuko 

Abstract

The sebaceous gland (SG) is an essential component of the skin, and SG dysfunction is debilitating1,2. Yet, the cellular bases for its origin, development and subsequent maintenance remain poorly understood. Here, we apply large-scale quantitative fate mapping to define the patterns of cell fate behaviour during SG development and maintenance. We show that the SG develops from a defined number of lineage-restricted progenitors that undergo a programme of independent and stochastic cell fate decisions. Following an expansion phase, equipotent progenitors transition into a phase of homeostatic turnover, which is correlated with changes in the mechanical properties of the stroma and spatial restrictions on gland size. Expression of the oncogene KrasG12D results in a release from these constraints and unbridled gland expansion. Quantitative clonal fate analysis reveals that, during this phase, the primary effect of the Kras oncogene is to drive a constant fate bias with little effect on cell division rates. These findings provide insight into the developmental programme of the SG, as well as the mechanisms that drive tumour progression and gland dysfunction.

Description

Keywords

Animals, Cell Proliferation, Disease Progression, Gene Expression Regulation, Developmental, Homeostasis, Mice, Transgenic, Stem Cells

Journal Title

Nat Cell Biol

Conference Name

Journal ISSN

1465-7392
1476-4679

Volume Title

21

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Wellcome Trust (098357/Z/12/Z)
Royal Society (RP/R1/180165)
European Commission Horizon 2020 (H2020) Societal Challenges (668294-2 INTENS)
Medical Research Council (MC_PC_12009)
Wellcome Trust Royal Society