Journal
NATURE CELL BIOLOGY
Volume 20, Issue 6, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41556-018-0108-1
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Funding
- Paris Sciences et Lettres (PSL* Research University)
- French National Research Agency (ANR) [ANR-15-CE13-0013-01]
- Canceropole Ile-de-France [2015-2-APD-01-ICR-1]
- Fondation de France
- Trinity College (Cambridge University)
- Sir Henry Wellcome Fellowship from the Wellcome Trust
- Bettencourt-Schueller Young Researcher Prize
- France-BioImaging [ANR-10-INBS-04]
- ERC ZEBRATECTUM [311159]
- ARC [SFI20121205686]
- Schlumberger Foundation
- Labex DEEP ANR [11-LBX-0044]
- Wellcome Trust [098357/Z/12/Z, 110326/Z/15/Z]
- [ANR-11 BSV2 012 01]
- Wellcome Trust [110326/Z/15/Z] Funding Source: Wellcome Trust
- European Research Council (ERC) [311159] Funding Source: European Research Council (ERC)
- Agence Nationale de la Recherche (ANR) [ANR-15-CE13-0013] Funding Source: Agence Nationale de la Recherche (ANR)
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Recent lineage tracing studies have revealed that mammary gland homeostasis relies on unipotent stem cells. However, whether and when lineage restriction occurs during embryonic mammary development, and which signals orchestrate cell fate specification, remain unknown. Using a combination of in vivo clonal analysis with whole mount immunofluorescence and mathematical modelling of clonal dynamics, we found that embryonic multipotent mammary cells become lineage-restricted surprisingly early in development, with evidence for unipotency as early as E12.5 and no statistically discernable bipotency after E15.5. To gain insights into the mechanisms governing the switch from multipotency to unipotency, we used gain-of-function Notch1 mice and demonstrated that Notch activation cell autonomously dictates luminal cell fate specification to both embryonic and basally committed mammary cells. These functional studies have important implications for understanding the signals underlying cell plasticity and serve to clarify how reactivation of embryonic programs in adult cells can lead to cancer.
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