Clonal analysis of Notch1-expressing cells reveals the existence of unipotent stem cells that retain long-term plasticity in the embryonic mammary gland.

Autor: Lilja AM; Institut Curie, PSL Research University, INSERM, CNRS, Paris, France.; Sorbonne University, UPMC University of Paris VI, Paris, France., Rodilla V; Institut Curie, PSL Research University, INSERM, CNRS, Paris, France. vrodilla@vhio.net.; Sorbonne University, UPMC University of Paris VI, Paris, France. vrodilla@vhio.net.; Preclinical Research Program; Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. vrodilla@vhio.net., Huyghe M; Institut Curie, PSL Research University, INSERM, CNRS, Paris, France.; Sorbonne University, UPMC University of Paris VI, Paris, France., Hannezo E; Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, UK.; The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK.; The Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK.; Institute of Science and Technology Austria, Klosterneuburg, Austria., Landragin C; Institut Curie, PSL Research University, INSERM, CNRS, Paris, France.; Sorbonne University, UPMC University of Paris VI, Paris, France., Renaud O; Institut Curie, PSL Research University, INSERM, CNRS, Paris, France.; Sorbonne University, UPMC University of Paris VI, Paris, France.; Cell and Tissue Imaging Facility (PICT-IBiSA), Institut Curie, Paris, France., Leroy O; Institut Curie, PSL Research University, INSERM, CNRS, Paris, France.; Sorbonne University, UPMC University of Paris VI, Paris, France.; Cell and Tissue Imaging Facility (PICT-IBiSA), Institut Curie, Paris, France., Rulands S; Max Planck Institute for the Physics of Complex Systems, Dresden, Germany.; Center for Systems Biology Dresden, Dresden, Germany., Simons BD; Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, UK.; The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK.; The Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK., Fre S; Institut Curie, PSL Research University, INSERM, CNRS, Paris, France. silvia.fre@curie.fr.; Sorbonne University, UPMC University of Paris VI, Paris, France. silvia.fre@curie.fr.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2018 Jun; Vol. 20 (6), pp. 677-687. Date of Electronic Publication: 2018 May 21.
DOI: 10.1038/s41556-018-0108-1
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz: