Proof of region-specific multipotent progenitors in human breast epithelia

Agla J Fridriksdottir; René Villadsen; Mikkel Morsing; Marie Christine Klitgaard; Jiyoung Kim; Ole William Petersen; Lone Rønnov-Jessen

doi:10.1073/pnas.1714063114

Proof of region-specific multipotent progenitors in human breast epithelia

Agla J Fridriksdottir, René Villadsen, Mikkel Morsing, Marie Christine Klitgaard, Jiyoung Kim, Ole William Petersen, Lone Rønnov-Jessen

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Abstract

The human breast parenchyma consists of collecting ducts and terminal duct lobular units (TDLUs). The TDLU is the site of origin of most breast cancers. The reason for such focal susceptibility to cancer remains poorly understood. Here, we take advantage of a region-specific heterogeneity in luminal progenitors to interrogate the differentiation repertoire of candidate stem cells in TDLUs. We show that stem-like activity in serial passage culture and in vivo breast morphogenesis relies on the preservation of a myoepithelial phenotype. By enrichment for region-specific progenitors, we identify bipotent and multipotent progenitors in ducts and TDLUs, respectively. We propose that focal breast cancer susceptibility, at least in part, originates from region-specific myoepithelial progenitors.

Originalsprog	Engelsk
Tidsskrift	Proceedings of the National Academy of Sciences of the United States of America
Vol/bind	114
Udgave nummer	47
Sider (fra-til)	E10102–E10111
ISSN	0027-8424
DOI	https://doi.org/10.1073/pnas.1714063114
Status	Udgivet - 21 nov. 2017

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10.1073/pnas.1714063114Licens: CC BY-NC-ND

Proof of region-specific multipotent progenitors in human breast epitheliaForlagets udgivne version, 2,84 MBLicens: CC BY-NC-ND

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AU - Fridriksdottir, Agla J

AU - Villadsen, René

AU - Morsing, Mikkel

AU - Klitgaard, Marie Christine

AU - Kim, Jiyoung

AU - Petersen, Ole William

AU - Rønnov-Jessen, Lone

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N2 - The human breast parenchyma consists of collecting ducts and terminal duct lobular units (TDLUs). The TDLU is the site of origin of most breast cancers. The reason for such focal susceptibility to cancer remains poorly understood. Here, we take advantage of a region-specific heterogeneity in luminal progenitors to interrogate the differentiation repertoire of candidate stem cells in TDLUs. We show that stem-like activity in serial passage culture and in vivo breast morphogenesis relies on the preservation of a myoepithelial phenotype. By enrichment for region-specific progenitors, we identify bipotent and multipotent progenitors in ducts and TDLUs, respectively. We propose that focal breast cancer susceptibility, at least in part, originates from region-specific myoepithelial progenitors.

AB - The human breast parenchyma consists of collecting ducts and terminal duct lobular units (TDLUs). The TDLU is the site of origin of most breast cancers. The reason for such focal susceptibility to cancer remains poorly understood. Here, we take advantage of a region-specific heterogeneity in luminal progenitors to interrogate the differentiation repertoire of candidate stem cells in TDLUs. We show that stem-like activity in serial passage culture and in vivo breast morphogenesis relies on the preservation of a myoepithelial phenotype. By enrichment for region-specific progenitors, we identify bipotent and multipotent progenitors in ducts and TDLUs, respectively. We propose that focal breast cancer susceptibility, at least in part, originates from region-specific myoepithelial progenitors.

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M3 - Journal article

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JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

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ER -

Proof of region-specific multipotent progenitors in human breast epithelia

Abstract

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