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SUMMARY:Extrinsic regulation of haematopoietic stem cell self - Sean J. Mo
 rrison Investigator\, Howard Hughes Medical Institute
DTSTART:20140715T104500Z
DTEND:20140715T123000Z
UID:TALK53327@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:We have historically studied the intrinsic mechanisms that reg
 ulate stem cell self-renewal and tissue regeneration\, focusing on the hae
 matopoietic and nervous systems. In the past few years we have expanded th
 e scope of these studies to include the extrinsic mechanisms that regulate
  haematopoietic stem cell self-renewal. By using functional genetic approa
 ches in vivo\, we have identified the cells in the bone marrow that are th
 e physiologically important sources of factors that promote HSC maintenanc
 e. Contrary to the dogma of an osteoblastic niche\, these studies demonstr
 ated that HSCs reside in a perivascular niche in which endothelial cells a
 nd Leptin Receptor-expressing mesenchymal stromal cells secrete multiple k
 ey factors that promote HSC maintenance\, including Stem Cell Factor and C
 xcl12 (Nature 481:457\; Nature 495:231\; Nature 505:327). We have shown th
 at this perivascular niche is necessary for the maintenance of quiescent H
 SCs (Cell Stem Cell 13:102) and that the microenvironment within this nich
 e collaborates with long-range signals\, such as estrogen\, to regulate HS
 C function in response to both local changes within the tissue as well as 
 overall physiological state (Nature 505:555). Finally\, the LepR+ stromal 
 cells that represent the major source of factors for HSC maintenance are a
 lso highly enriched for mesenchymal stem cells (MSCs) and are the major so
 urce of new bone and adipocytes that form throughout adult life in the bon
 e marrow. New imaging approaches that we are developing enable high-throug
 hput imaging of HSCs and their interactions with stromal cells throughout 
 the three dimensional bone marrow compartment with confocal resolution.\n
LOCATION:Max Perutz Lecture Theatre\, Medical Research Council (MRC) (MRC 
 Laboratory of Molecular Biol
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