Adipocyte progenitors are primary contributors to the disrupted epithelial niche that is sustained following abrupt mammary gland involution
Joshi, P. A.; Nuthalapati, P.; Maiti, D.; Kwende, S.; Maity, S.; Ning, D.
Show abstract
A short duration of breastfeeding is a risk factor for the development of high-mortality, postpartum, triple-negative breast cancer. The intrinsic properties of cancer-initiating epithelial cells that persist following breastfeeding cessation and mammary gland remodeling are poorly understood. Previously, we showed that Platelet-Derived Growth Factor Receptor alpha (PDGFR)-expressing stromal mammary adipocyte progenitors (MAPs) differentiate into epithelial luminal progenitors in the adult gland. In the current study, we demonstrate that MAP-derived luminal progenitors retain a mesenchymal transcriptomic signature. In an abrupt involution model that mimics a short breastfeeding duration, MAP-derived luminal progenitors persist and dominate luminal epithelia, undergoing transcriptomic alterations that signify a distinct ferrometabolic state linked to cancer. Concurrently, MAPs adopt an alternative interferon-mediated profibrotic and invasive stromal fate. Our work uncovers MAPs to be the primary cellular origin of a pathological stromal and epithelial microenvironment following abrupt involution, presenting a potential therapeutic target in postpartum breast cancer.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Transcriptional changes in the mammary gland during lactation revealed by single cell sequencing of cells from human milk 97%
- Influence of genetic ancestry on breast stromal cells provides biologic basis for increased incidence of metaplastic breast cancer in women of African descent 96%
- Pre-ciliated tubal epithelial cells are prone to initiation of high-grade serous ovarian carcinoma 96%
Similar papers in this journal
- Aging-associated alterations in the mammary gland revealed by single-cell RNA sequencing 95%
- Single cell transcriptomics reveals involution mimicry during the specification of the basal breast cancer subtype 95%
- Parity-induced changes to mammary epithelial cells control NKT cell expansion and mammary oncogenesis 95%
Similar papers in this journal
- An EMT-primary cilium-GLIS2 signaling axis regulates mammogenesis and claudin-low breast tumorigenesis 94%
- Transcriptome and regulatory maps of decidua-derived stromal cells inform gene discovery in preterm birth 93%
- Defining metabolic flexibility in hair follicle stem cell induced squamous cell carcinoma 92%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.