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SEMINAR: Bayliss Seminar Series

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Today's date is Wednesday, January 20, 2021
Bayliss Seminar Series : Human milk cells as a tool to decipher mammary gland biology Other events...
The human mammary gland (MG) is unique in that it fully matures only in pregnancy and lactation, and has the ability to do so repeatedly during life. The function of the gland is to synthesise, secrete and deliver milk specifically for the nourishment, development and protection of the offspring. The aim of my PhD was to provide insight into the changes occurring in this organ at the cellular and molecular levels to facilitate successful lactation. Towards this end, cells isolated from prepartum mammary secretions (PS) during late pregnancy as well as human milk (HM) samples collected during lactation were utilised as a tool to non-invasively access the cellular hierarchy of the developing and the functional MG, respectively. First, global gene expression was examined in cells from longitudinal samples collected in pregnancy and across lactation from the same individuals to establish changes during normal development. Numerous genes previously considered as “lactation” genes in animal studies were confirmed in the PS and HM cells and novel pathways were identified characterising changes occurring in the MG during pregnancy, such as cell adhesion, and morphological changes occurring during lactation. Differences in gene expression between women were further examined using a subset of selected key genes in HM cells cross-sectionally to explore variation in the population and potential associations with mother/infant demographic characteristics. High expression of ESRRB, CK5 and CK14 were observed across women and correlations between the lactocyte marker CK18 and maternal body mass index (BMI) may provide a potential mechanism behind breastfeeding difficulties in obese women. Further, key genes with important functions either in the normal resting MG or in the cancer affected organ were examined in the longitudinal PS and HM cell data set to determine their normal expression in the developing and functional MG. Normal luminal progenitor cell signatures were dominant in the HM cells and genes associated with the stem-like intrinsic breast cancer subtype claudin-low were found to be highly expressed both during pregnancy and lactation, highlighting the presence of stem cells in the normal MG development and function. Identification of specific neurotrophin signalling receptors previously associated with cancer in the PS and HM cells was also found. Tyrosine receptor kinase B (TrkB) was differentially regulated and p75 significantly downregulated during pregnancy and lactation, whereas sortilin was consistently expressed across different stages of MG development suggesting targeted regulation. The studies described here improve the current understanding of the changing landscape of the mammary cellular composition during pregnancy and lactation, the variation between women and potential molecular associations, and the involvement of cancer-related genes in the normal development of the MG.
Speaker(s) Alecia-Jane Twigger
Location Bayliss Building, G33
Contact The School of Chemistry and Biochemistry Team <[email protected]> : 6488 4402
Start Thu, 20 Oct 2016 12:00
End Thu, 20 Oct 2016 12:45
Submitted by scbevents <[email protected]>
Last Updated Mon, 10 Oct 2016 16:31
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