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Reconstitution of mammary epithelial morphogenesis by murine embryonic stem cells undergoing hematopoietic stem cell differentiation

Jiang, S and Lee, BC and Fu, Y and Avraham, S and Lim, B and Avraham, HK (2010) Reconstitution of mammary epithelial morphogenesis by murine embryonic stem cells undergoing hematopoietic stem cell differentiation. PLoS ONE, 5 (3).

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Background: Mammary stem cells are maintained within specific microenvironments and recruited throughout lifetime to reconstitute de novo the mammary gland. Mammary stem cells have been isolated through the identification of specific cell surface markers and in vivo transplantation into cleared mammary fat pads. Accumulating evidence showed that during the reformation of mammary stem cell niches by dispersed epithelial cells in the context of the intact epithelium-free mammary stroma, non-mammary epithelial cells may be sequestered and reprogrammed to perform mammary epithelial cell functions and to adopt mammary epithelial characteristics during reconstruction of mammary epithelium in regenerating mammary tissue in vivo. Methodology/Principal Findings: To examine whether other types of progenitor cells are able to contribute to mammary branching morphogenesis, we examined the potential of murine embryonic stem (mES) cells, undergoing hematopoietic differentiation, to support mammary reconstitution in vivo. We observed that cells from day 14 embryoid bodies (EBs) under hematopoietic differentiation condition, but not supernatants derived from these cells, when transplanted into denuded mammary fat pads, were able to contribute to both the luminal and myoepithelial lineages in branching ductal structures resembling the ductal-alveolar architecture of the mammary tree. No teratomas were observed when these cells were transplanted in vivo. Conclusions/Significance: Our data provide evidence for the dominance of the tissue-specific mammary stem cell niche and its role in directing mES cells, undergoing hematopoietic differentiation, to reprogram into mammary epithelial cells and to promote mammary epithelial morphogenesis. These studies should also provide insights into regeneration of damaged mammary gland and the role of the mammary microenvironment in reprogramming cell fate. © 2010 Jiang et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Jiang, S
Lee, BC
Fu, Y
Avraham, S
Lim, B
Avraham, HK
ContributionContributors NameEmailPitt UsernameORCID
Centers: Other Centers, Institutes, Offices, or Units > Hillman Cancer Center
Date: 1 December 2010
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 5
Number: 3
DOI or Unique Handle: 10.1371/journal.pone.0009707
Refereed: Yes
MeSH Headings: Animals; Cell Differentiation; Cell Lineage; Collagen--chemistry; Drug Combinations; Embryonic Stem Cells--cytology; Green Fluorescent Proteins--chemistry; Green Fluorescent Proteins--metabolism; Hematopoiesis; Hematopoietic Stem Cells--cytology; Immunohistochemistry--methods; Laminin--chemistry; Mammary Glands, Animal--metabolism; Mice; Mice, Inbred BALB C; Polymerase Chain Reaction; Proteoglycans--chemistry; Time Factors; Y Chromosome
Other ID: NLM PMC2837751
PubMed Central ID: PMC2837751
PubMed ID: 20300573
Date Deposited: 03 Aug 2012 18:44
Last Modified: 02 Feb 2019 16:58


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