title: The transcriptional repressor Blimp1 is expressed in rare luminal progenitors and is essential for mammary gland development.
abstract: 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.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
authors.forename: Mohammed I
authors.initials: MI
authors.lastname: Ahmed
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
authors.forename: Salah
authors.identifier: 0000-0003-1005-438X
authors.initials: S
authors.lastname: Elias
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
authors.forename: Arne W
authors.initials: AW
authors.lastname: Mould
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Bikoff
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK elizabeth.robertson@path.ox.ac.uk.
authors.forename: Elizabeth J
authors.identifier: 0000-0001-6562-0225
authors.initials: EJ
authors.lastname: Robertson
mesh_terms: D000818:Animals; D002451:Cell Compartmentation / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D002478:Cells, Cultured; D002999:Clone Cells; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006728:Hormones / Q000494:pharmacology; D007774:Lactation / Q000187:drug effects; D008321:Mammary Glands, Animal / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009024:Morphogenesis / Q000187:drug effects; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011247:Pregnancy; D012097:Repressor Proteins / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D013256:Steroids / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D006728:Hormones; C513258:Prdm1 protein, mouse; D012097:Repressor Proteins; D013256:Steroids; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1
keywords: 3D culture; Blimp1; Lumen formation; Luminal progenitors; Mammary gland morphogenesis; Mouse; Polarity; Prdm1; Transcriptional repressor