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SUMMARY:‘Mammary epithelial cell fate and tumour initiation at the singl
 e cell resolution’ - Walid Khaled\, Department of Pharmacology\, Univers
 ity of Cambridge
DTSTART:20190409T103000Z
DTEND:20190409T113000Z
UID:TALK121780@talks.cam.ac.uk
CONTACT:Mala Jayasundera
DESCRIPTION:*Abstract:*\n\nCharacterising the hierarchy of mammary epithel
 ial cells (MECs) and how they are regulated during adult development is im
 portant for understanding how breast cancer arises. Recently we used singl
 e-cell RNA sequencing (scRNAseq) to determine the gene expression profile 
 of MECs across adult developmental stages. However\, little is known about
  how during the early stages of breast cancer development\, specific genet
 ic aberrations impact the fate of MECs. In this talk I will describe our r
 ecent work where we identify the earliest cellular change in the mammary g
 land during triple negative breast cancer (TNBC) development. In this stud
 y\, we examine the interplay between the TNBC oncogene\, BCL11A\, and the 
 putative cell of origin\, luminal progenitors. We demonstrate that the del
 etion of Bcl11a completely protects the Brca1/p53 TNBC mouse model from de
 veloping tumours. scRNAseq analysis of pre-cancerous tissue reveals that B
 cl11a deletion fully reverses an aberrant differentiation behaviour of lum
 inal progenitor cells. As such\, our data demonstrates that Bcl11a is an e
 ssential oncogene in TNBC due to its critical role in enabling the cell of
  origin to aberrantly differentiate during early stages of tumour initiati
 on. Finally\, I will describe how we are expanding the use of single cell 
 genomic approaches to understand changes in the Tumour Microenvironment (T
 ME) during the various stages of tumour development. Collectively our data
  sheds light on the cellular changes during early stages of tumour develop
 ment with potential implications for early detection and therapeutic inter
 vention.\n
LOCATION:Sackler Lecture Theatre (Level 7)\, Cambridge Institute for Medic
 al Research
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