Abstract #302
Section: Lactation Biology (orals)
Session: Lactation Biology Symposium: Refining the Old to Answer the New: Moving Approaches Forward to Study Mammary and Lactation Physiology
Format: Oral
Day/Time: Tuesday 11:45 AM–12:30 PM
Location: Junior Ballroom C
Session: Lactation Biology Symposium: Refining the Old to Answer the New: Moving Approaches Forward to Study Mammary and Lactation Physiology
Format: Oral
Day/Time: Tuesday 11:45 AM–12:30 PM
Location: Junior Ballroom C
# 302
Deep tissue imaging of lobuloalveolar development in the mouse.
C. J. Watson*1, 1Department of Pathology, University of Cambridge, Cambridge, UK.
Speaker Bio
Deep tissue imaging of lobuloalveolar development in the mouse.
C. J. Watson*1, 1Department of Pathology, University of Cambridge, Cambridge, UK.
The pregnancy/lactation/involution cycle of mammary gland development requires the rapid proliferation and subsequent differentiation of both luminal and basal epithelial cells that are presumed to arise from stem cells. To investigate this process, we utilized 2 neutral lineage tracing approaches coupled with new protocols for clearing of mammary tissue to allow deep 3-dimensional (3D) confocal imaging. By labeling stem cells at clonal density we were able to show that individual alveoli arise from unipotent basal and luminal stem cells and that more than one stem cell of each lineage is required to generate an entire alveolus. Furthermore, 3D imaging revealed the presence of multiple binucleate cells in the lactating gland suggesting failed cytokinesis. In addition, deep imaging with antibodies to smooth muscle actin and keratin 14 revealed the distinctive structure of basal cells in alveoli compared with ducts and allowed the collapse of alveoli during involution to be monitored. Surprisingly, we discovered an intimate and dynamic association of leukocytes with the epithelium and have analyzed these further by flow cytometry.
Speaker Bio
Christine studied Biochemistry at the University of Glasgow and obtained her PhD in Molecular Genetics at Imperial College London in Peter Rigby’s laboratory. Following postdoctoral work with Ron Hay at St Andrews University and the late John Clarke at the Roslin Institute, Christine was awarded an AFRC (now BBSRC) personal fellowship to set up her own laboratory where the focus was on transcriptional regulation of milk protein gene expression and the role of cell death in mammary gland, in collaboration with Andrew Wyllie. Following a re-location to the University of Cambridge in 1998, the focus was broadened to include the generation of complex 3D models of mammary gland, the role of the lysosome in cell death regulation, and the clonal analysis of mammary stem and progenitor cells using deep 3D imaging. Current work utilises mammary organoids and CRISPR/Cas9 technology to ablate components of specific signalling pathways. Christine is a Fellow of the Academy of Medical Sciences and a member of the Nuffield Council on Bioethics.
