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Title: Human mammary progenitor cell fate decisions are products of interactions with combinatorial microenvironments

Abstract

In adult tissues, multi-potent progenitor cells are some of the most primitive members of the developmental hierarchies that maintain homeostasis. That progenitors and their more mature progeny share identical genomes, suggests that fate decisions are directed by interactions with extrinsic soluble factors, ECM, and other cells, as well as physical properties of the ECM. To understand regulation of fate decisions, therefore, would require a means of understanding carefully choreographed combinatorial interactions. Here we used microenvironment protein microarrays to functionally identify combinations of cell-extrinsic mammary gland proteins and ECM molecules that imposed specific cell fates on bipotent human mammary progenitor cells. Micropatterned cell culture surfaces were fabricated to distinguish between the instructive effects of cell-cell versus cell-ECM interactions, as well as constellations of signaling molecules; and these were used in conjunction with physiologically relevant 3 dimensional human breast cultures. Both immortalized and primary human breast progenitors were analyzed. We report on the functional ability of those proteins of the mammary gland that maintain quiescence, maintain the progenitor state, and guide progenitor differentiation towards myoepithelial and luminal lineages.

Authors:
; ; ; ; ; ; ;
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
Life Sciences Division
OSTI Identifier:
986922
Report Number(s):
LBNL-3871E
Journal ID: 1093-4391; TRN: US201018%%149
DOE Contract Number:  
DE-AC02-05CH11231; R01CA064786
Resource Type:
Journal Article
Journal Name:
Integrative Biology
Additional Journal Information:
Journal Volume: 1; Journal Issue: 1; Related Information: Journal Publication Date: January 2009
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ADULTS; CELL CULTURES; FUNCTIONALS; HOMEOSTASIS; MAMMARY GLANDS; PHENOBARBITAL; PHYSICAL PROPERTIES; PROGENY; PROTEINS; REGULATIONS

Citation Formats

LaBarge, Mark A, Nelson, Celeste M, Villadsen, Rene, Fridriksdottir, Agla, Ruth, Jason R, Stampfer, Martha R, Petersen, Ole W, and Bissell, Mina J. Human mammary progenitor cell fate decisions are products of interactions with combinatorial microenvironments. United States: N. p., 2008. Web.
LaBarge, Mark A, Nelson, Celeste M, Villadsen, Rene, Fridriksdottir, Agla, Ruth, Jason R, Stampfer, Martha R, Petersen, Ole W, & Bissell, Mina J. Human mammary progenitor cell fate decisions are products of interactions with combinatorial microenvironments. United States.
LaBarge, Mark A, Nelson, Celeste M, Villadsen, Rene, Fridriksdottir, Agla, Ruth, Jason R, Stampfer, Martha R, Petersen, Ole W, and Bissell, Mina J. Fri . "Human mammary progenitor cell fate decisions are products of interactions with combinatorial microenvironments". United States. https://www.osti.gov/servlets/purl/986922.
@article{osti_986922,
title = {Human mammary progenitor cell fate decisions are products of interactions with combinatorial microenvironments},
author = {LaBarge, Mark A and Nelson, Celeste M and Villadsen, Rene and Fridriksdottir, Agla and Ruth, Jason R and Stampfer, Martha R and Petersen, Ole W and Bissell, Mina J},
abstractNote = {In adult tissues, multi-potent progenitor cells are some of the most primitive members of the developmental hierarchies that maintain homeostasis. That progenitors and their more mature progeny share identical genomes, suggests that fate decisions are directed by interactions with extrinsic soluble factors, ECM, and other cells, as well as physical properties of the ECM. To understand regulation of fate decisions, therefore, would require a means of understanding carefully choreographed combinatorial interactions. Here we used microenvironment protein microarrays to functionally identify combinations of cell-extrinsic mammary gland proteins and ECM molecules that imposed specific cell fates on bipotent human mammary progenitor cells. Micropatterned cell culture surfaces were fabricated to distinguish between the instructive effects of cell-cell versus cell-ECM interactions, as well as constellations of signaling molecules; and these were used in conjunction with physiologically relevant 3 dimensional human breast cultures. Both immortalized and primary human breast progenitors were analyzed. We report on the functional ability of those proteins of the mammary gland that maintain quiescence, maintain the progenitor state, and guide progenitor differentiation towards myoepithelial and luminal lineages.},
doi = {},
journal = {Integrative Biology},
number = 1,
volume = 1,
place = {United States},
year = {2008},
month = {9}
}