LPA receptor activity is basal specific and coincident with early pregnancy and involution during mammary gland postnatal development.
During pregnancy, luminal and basal epithelial cells of the adult mammary gland proliferate and differentiate resulting in remodeling of the adult gland. While pathways that control this process have been characterized in the gland as a whole, the contribution of specific cell subtypes, in particular the basal compartment, remains largely unknown. Basal cells provide structural and contractile support, however they also orchestrate the communication between the stroma and the luminal compartment at all developmental stages. Using RNA-seq, we show that basal cells are extraordinarily transcriptionally dynamic throughout pregnancy when compared to luminal cells. We identified gene expression changes that define specific basal functions acquired during development that led to the identification of novel markers. Enrichment analysis of gene sets from 24 mouse models for breast cancer pinpoint to a potential new function for insulin-like growth factor 1 (Igf1r) in the basal epithelium during lactogenesis. We establish that β-catenin signaling is activated in basal cells during early pregnancy, and demonstrate that this activity is mediated by lysophosphatidic acid receptor 3 (Lpar3). These findings identify novel pathways active during functional maturation of the adult mammary gland.
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Deanna
D
Acosta
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Susmita
S
Bagchi
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Pilib Ó
PÓ
Broin
Department of Physiology, Michigan State University, East Lansing, MI, 48824, USA.
Daniel
D
Hollern
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Silvia E
SE
Racedo
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Bernice
B
Morrow
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Rani S
RS
Sellers
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
John M
JM
Greally
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Aaron
A
Golden
Department of Physiology, Michigan State University, East Lansing, MI, 48824, USA.
Eran
E
Andrechek
Department of Neurology and Neuroscience, Rutgers New Jersey Medical School, Newark, NJ, 07101, USA.
Teresa
T
Wood
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.|Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Cristina
C
Montagna
D000818:Animals; D019070:Cell Lineage / Q000235:genetics*; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D007774:Lactation / Q000502:physiology*; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D038081:Organogenesis / Q000502:physiology*; D011247:Pregnancy; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D051176:beta Catenin; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I