TY - JOUR
T1 - Proof of region-specific multipotent progenitors in human breast epithelia
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
N1 - Copyright © 2017 the Author(s). Published by PNAS.
PY - 2017
Y1 - 2017
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.
KW - Journal Article
U2 - 10.1073/pnas.1714063114
DO - 10.1073/pnas.1714063114
M3 - Journal article
C2 - 29109259
VL - 114
SP - E10102–E10111
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
SN - 0027-8424
IS - 47
ER -