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SUMMARY:The intrinsic and extrinsic regulation of stem cells self-renewal 
 - Sean J Morrison\, Children’s Research Institute\, University of Texas 
 Southwestern Medical Center
DTSTART:20111117T130000Z
DTEND:20111117T140000Z
UID:TALK27048@talks.cam.ac.uk
CONTACT:Kate Davenport
DESCRIPTION:We have identified networks of proto-oncogenes and tumor suppr
 essors that act intrinsically within stem cells to regulate their maintena
 nce throughout life in the hematopoietic and nervous systems. We recently 
 discovered that evolutionarily conserved heterochronic genes coordinate ch
 anges in these networks with age\, that control changes in stem cell prope
 rties between fetal\, young adult\, and old adult stages. These mechanisms
  begin to explain how stem cell properties can change over time in a way t
 hat is appropriate to the changing growth and regeneration demands of tiss
 ues\, as well as the increasing risk of neoplastic transformation with age
 .\nOur work on the extrinsic regulation of stem cell function has focused 
 on the characterization of the hematopoietic stem cell (HSC) niche. We dem
 onstrated that most HSCs reside adjacent to sinusoidal blood vessels in th
 e bone marrow. However\, a number of cell types have been proposed to crea
 te niches for HSCs and the expression patterns of HSC maintenance factors 
 have not been systematically studied. No HSC maintenance factor has been c
 onditionally deleted from any candidate niche cell. Thus\, the identities 
 of the cells that are physiologically important sources of the factors tha
 t promote HSC maintenance in vivo remain untested. Stem Cell Factor (SCF) 
 is non-autonomously required for HSC maintenance and is a key component of
  the niche. Using Scfgfp knock-in mice we found Scf was primarily expresse
 d by endothelial and perivascular stromal cells throughout the bone marrow
 . Using Scffl mice\, we found that HSC frequency and function were not aff
 ected when Scf was conditionally deleted from hematopoietic cells\, osteob
 lasts\, or Nestin-Cre-expressing stromal cells. However\, HSCs were deplet
 ed from the bone marrow when Scf was deleted from endothelial cells or Lep
 tin receptor-expressing perivascular stromal cells. Therefore\, HSCs resid
 e in a perivascular niche in which multiple cell types secrete factors tha
 t promote HSC maintenance.\n
LOCATION:Cancer Research UK Cambridge Research Institute\, Lecture Theatre
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