Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/19118
Título
Luminal Rank loss decreases cell fitness leading to basal cell bipotency in parous mammary glands.
Autor(es)
Fecha de publicación
2023-10-09
Cita
Nat Commun. 2023;14(1):6213.
Idioma
Inglés
Tipo de documento
journal article
Resumen
Rank signaling pathway regulates mammary gland homeostasis and epithelial cell differentiation. Although Rank receptor is expressed by basal cells and luminal progenitors, its role in each individual cell lineage remains unclear. By combining temporal/lineage specific Rank genetic deletion with lineage tracing techniques, we found that loss of luminal Rank reduces the luminal progenitor pool and leads to aberrant alveolar-like differentiation with high protein translation capacity in virgin mammary glands. These Rank-deleted luminal cells are unable to expand during the first pregnancy, leading to lactation failure and impairment of protein synthesis potential in the parous stage. The unfit parous Rank-deleted luminal cells in the alveoli are progressively replaced by Rank-proficient cells early during the second pregnancy, thereby restoring lactation. Transcriptomic analysis and functional assays point to the awakening of basal bipotency after pregnancy by the induction of Rank/NF-κB signaling in basal parous cell to restore lactation and tissue homeostasis.
MESH
Epithelial Cells | Stem Cells | Pregnancy | Female | Animals | Cell Differentiation | Cell Lineage | Signal Transduction | Mammary Glands, Animal
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DOI
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- Reporting Summary