The transcriptional repressor Blimp1 is expressed in rare luminal progenitors and is essential for mammary gland development

Mammary gland morphogenesis depends on a tight balance between cell proliferation, differentiation and apoptosis, to create a defined functional hierarchy within the epithelia. The limited availability of stem cell/progenitor markers has made it challenging to decipher lineage relationships. Here, w...

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Main Authors: I. Ahmed, M, Elias, S, Mould, A, Bikoff, E, Robertson, E
Format: Journal article
Published: Company of Biologists 2016
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author I. Ahmed, M
Elias, S
Mould, A
Bikoff, E
Robertson, E
author_facet I. Ahmed, M
Elias, S
Mould, A
Bikoff, E
Robertson, E
author_sort I. Ahmed, M
collection OXFORD
description Mammary gland morphogenesis depends on a tight balance between cell proliferation, differentiation and apoptosis, to create a defined functional hierarchy within the epithelia. The limited availability of stem cell/progenitor markers has made it challenging to decipher lineage relationships. Here, we identify a rare subset of luminal progenitors that express the zinc finger transcriptional repressor Blimp1, and demonstrate that this subset of highly clonogenic luminal progenitors is required for mammary gland development. Conditional inactivation experiments using K14-Cre and WAPi-Cre deleter strains revealed essential functions at multiple developmental stages. Thus, Blimp1 regulates proliferation, apoptosis and alveolar cell maturation during puberty and pregnancy. Loss of Blimp1 disrupts epithelial architecture and lumen formation both in vivo and in three-dimensional (3D) primary cell cultures. Collectively, these results demonstrate that Blimp1 is required to maintain a highly proliferative luminal subset necessary for mammary gland development and homeostasis.
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spelling oxford-uuid:728c2509-a501-41a2-8004-ed98d0d377f62022-03-26T19:50:49ZThe transcriptional repressor Blimp1 is expressed in rare luminal progenitors and is essential for mammary gland developmentJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:728c2509-a501-41a2-8004-ed98d0d377f6Symplectic Elements at OxfordCompany of Biologists2016I. Ahmed, MElias, SMould, ABikoff, ERobertson, EMammary gland morphogenesis depends on a tight balance between cell proliferation, differentiation and apoptosis, to create a defined functional hierarchy within the epithelia. The limited availability of stem cell/progenitor markers has made it challenging to decipher lineage relationships. Here, we identify a rare subset of luminal progenitors that express the zinc finger transcriptional repressor Blimp1, and demonstrate that this subset of highly clonogenic luminal progenitors is required for mammary gland development. Conditional inactivation experiments using K14-Cre and WAPi-Cre deleter strains revealed essential functions at multiple developmental stages. Thus, Blimp1 regulates proliferation, apoptosis and alveolar cell maturation during puberty and pregnancy. Loss of Blimp1 disrupts epithelial architecture and lumen formation both in vivo and in three-dimensional (3D) primary cell cultures. Collectively, these results demonstrate that Blimp1 is required to maintain a highly proliferative luminal subset necessary for mammary gland development and homeostasis.
spellingShingle I. Ahmed, M
Elias, S
Mould, A
Bikoff, E
Robertson, E
The transcriptional repressor Blimp1 is expressed in rare luminal progenitors and is essential for mammary gland development
title The transcriptional repressor Blimp1 is expressed in rare luminal progenitors and is essential for mammary gland development
title_full The transcriptional repressor Blimp1 is expressed in rare luminal progenitors and is essential for mammary gland development
title_fullStr The transcriptional repressor Blimp1 is expressed in rare luminal progenitors and is essential for mammary gland development
title_full_unstemmed The transcriptional repressor Blimp1 is expressed in rare luminal progenitors and is essential for mammary gland development
title_short The transcriptional repressor Blimp1 is expressed in rare luminal progenitors and is essential for mammary gland development
title_sort transcriptional repressor blimp1 is expressed in rare luminal progenitors and is essential for mammary gland development
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