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.affiliation: Lawrence Berkeley National Laboratory, Division of Life Sciences, Berkeley, CA 94720, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: LaBarge
authors.forename: Celeste M
authors.initials: CM
authors.lastname: Nelson
authors.forename: Rene
authors.initials: R
authors.lastname: Villadsen
authors.forename: Agla
authors.initials: A
authors.lastname: Fridriksdottir
authors.forename: Jason R
authors.initials: JR
authors.lastname: Ruth
authors.forename: Martha R
authors.initials: MR
authors.lastname: Stampfer
authors.forename: Ole W
authors.initials: OW
authors.lastname: Petersen
authors.forename: Mina J
authors.initials: MJ
authors.lastname: Bissell
mesh_terms: D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D002469:Cell Separation / Q000379:methods; D002470:Cell Survival; D002478:Cells, Cultured; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology* / Q000502:physiology*; D040081:Protein Array Analysis / Q000379:methods*; D020543:Proteome / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*
chemical_list: D020543:Proteome