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Neutral lineage tracing of proliferative embryonic and adult mammary stem/progenitor cells.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Lloyd-Lewis, Bethan  ORCID logo  https://orcid.org/0000-0001-6511-1818
Hitchcock, Jessica R 
Watson, Christine J  ORCID logo  https://orcid.org/0000-0002-8548-5902

Abstract

Mammary gland development occurs over multiple phases, beginning in the mammalian embryo and continuing throughout reproductive life. The remarkable morphogenetic capacity of the mammary gland at each stage of development is attributed to the activities of distinct populations of mammary stem cells (MaSCs) and progenitor cells. However, the relationship between embryonic and adult MaSCs, and their fate during different waves of mammary gland morphogenesis, remains unclear. By employing a neutral, low-density genetic labelling strategy, we characterised the contribution of proliferative stem/progenitor cells to embryonic, pubertal and reproductive mammary gland development. Our findings further support a model of lineage restriction of MaSCs in the postnatal mammary gland, and highlight extensive redundancy and heterogeneity within the adult stem/progenitor cell pool. Furthermore, our data suggest extensive multiplicity in their foetal precursors that give rise to the primordial mammary epithelium before birth. In addition, using a single-cell labelling approach, we revealed the extraordinary capacity of a single embryonic MaSC to contribute to postnatal ductal development. Together, these findings provide tantalising new insights into the disparate and stage-specific contribution of distinct stem/progenitor cells to mammary gland development.

Description

Keywords

Adult mammary stem cells, Embryonic mammary stem cells, Lineage tracing, Mammary gland development, Adult Stem Cells, Animals, Cell Lineage, Cell Proliferation, Embryonic Development, Mammary Glands, Animal, Mice, Morphogenesis, Mouse Embryonic Stem Cells, Sexual Maturation, Single-Cell Analysis

Journal Title

Development

Conference Name

Journal ISSN

0950-1991
1477-9129

Volume Title

145

Publisher

The Company of Biologists
Sponsorship
Medical Research Council (MR/J001023/1)
Medical Research Council (MR/N022963/1)
Medical Research Council (MC_PC_12009)
Wellcome Trust (105377/Z/14/Z)
This work was supported by the Medical Research Council [MR/J001023/1 to C.J.W. and B.L-L and MR/N022963/1 to C.J.W. and J.R.H], National Health and Medical Research Council [1071074 and 1141008 to F.M.D] and Wellcome Trust [105377/Z/14/Z to O.B.H].