136th iCeMS Seminar: Prof. Alan R Tall
Leukocytosis is a risk factor for athero-thrombotic disease in humans, and develops in
animal models of atherosclerosis in response to feeding high fat, high cholesterol diets.
The ATP binding cassette transporters ABCA1 and ABCG1 promote cholesterol e ux to
apoA-1 and HDL, respectively and are targets of LXR transcription factors. Mice lacking
ABCA1/G1 develop a dramatic myeloproliferative phenotype with monocytosis and
neutrophilia, associated with expansion and proliferation of hematopoietic stem and
myeloid progenitor populations (HSPCs). The transporters are highly expressed in
HSPCs where they act to control proliferative responses to growth factors (IL-3, GM-CSF)
by regulating plasma membrane lipid rafts and cell surface expression of the common
beta subunit of the IL-3/GM-CSF receptor. ABCG4 is closely related to ABCG1 but is
expressed primarily in the megakaryocyte progenitor (MkP) population of the bone
marrow. ABCG4 de cient mice have MkP proliferation and expansion, thrombocytosis,
increased platelet/leukocyte aggregates and accelerated atherosclerosis. ABCG4
promotes cholesterol e ux onto HDL, and thereby reduces the cell surface expression
of the thrombopoietin (TPO) receptor. Overall results suggest that ATP binding cassette
transporters promote cholesterol e ux, decrease membrane lipid raft formation and
enhance the feedback down-regulation of growth factor receptors in response to
growth factor binding, with anti-proliferative responses that may be bene cial in
atherosclerosis and myeloproliferative neoplasms.
(Nature Medicine, published online 14 April 2013; doi:10.1038/nm.3150)
| Lecturer |  Department of Medicine Columbia University, New York |
|---|---|
| Title | ABC transporters regulate hematopoietic stem and progenitor cell proliferation, leukocytosis, thrombocytosis and atherosclerosis |
| Date / Time | Tue, May 14, 2013 / 16:00-17:30 |
| Venue | CiRA (Center for iPS Cell Research and Application), 1F Auditorium, Kyoto University -> Directions |
| Flyer |  PDF (474KB) |
| Host |
Kyoto University Institute for Integrated Cell-Material Sciences (WPI-iCeMS) Center for Frontier Medicine, Global COE Program, Kyoto University |
| Co-host | Kyoto University's Global COE Program: Center for Frontier Medicine |
| Contact | iCeMS Ueda Lab | ueda-g@icems.kyoto-u.ac.jp |