Aging alters transcriptional circuitries and SLUG-mediated cellular states of mouse mammary epithelium.
Gross, Kayla.
2019
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Age-associated decline in stem cell function predisposes
tissues to dysfunction and disease and is driven by disruption of cellular
homeostasis. The bulk of age-associated changes to the mammary epithelial
epithelium and its stem/progenitor compartments have been studied after the
onset of reproductive senescence (menopause) that occurs around midlife, yet
nearly half of women in the U.S. are ... read morediagnosed with breast cancer before age
62, suggesting that age-associated risk factors for breast cancer
development are already present before or after midlife. As such, we sought
to investigate the consequences of perimenopausal transition on mammary
tissue and stem cell biology. Here we show that middle-aged, perimenopausal
mice exhibit facultative stem cell decline, aberrant luminal differentiation
in basal cells, and increased genomic and protein stress. Additionally, we
demonstrate that young adult mice lacking the transcription factor
SLUG/SNAI2 exhibit many of the molecular and cellular features of
perimenopause, including facultative stem cell decline, aberrant luminal
differentiation in basal cells, and increased DNA damage. Collectively,
these results show that the transition to menopause triggers cellular stress
that leads to stem cell decline, which is phenocopied by SLUG loss. These
findings also link a transcription factor that controls stem cell activity
and cell identity to DNA repair and aging.
Thesis (Ph.D.)--Tufts University, 2019.
Submitted to the Dept. of Cell, Molecular & Developmental Biology.
Advisor: Charlotte Kuperwasser.
Committee: Karl Munger, James Schwob, and Lidija Covic.
Keyword: Cellular biology.read less - ID:
- r207v2619
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- TARC Citation Guide EndNote
