第136回 アイセムスセミナー：Alan R Tall教授

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 eux 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 decient mice have MkP proliferation and expansion, thrombocytosis, increased platelet/leukocyte aggregates and accelerated atherosclerosis. ABCG4 promotes cholesterol eux onto HDL, and thereby reduces the cell surface expression of the thrombopoietin (TPO) receptor. Overall results suggest that ATP binding cassette transporters promote cholesterol eux, 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 benecial in atherosclerosis and myeloproliferative neoplasms.
(Nature Medicine, published online 14 April 2013; doi:10.1038/nm.3150)

講演者	Alan R Tall 教授 米コロンビア大学 分子医学研究科
演題	ABC transporters regulate hematopoietic stem and progenitor cell proliferation, leukocytosis, thrombocytosis and atherosclerosis
日時	2013年5月14日（火 ）16:00-17:30
場所	京都大学 iPS細胞研究所(CiRA）1階 オーディトリアム →アクセスマップ
フライヤー	PDF (474KB)
主催	京都大学 物質－細胞統合システム拠点（iCeMS＝アイセムス）
共催	京都大学医学研究科グローバルCOEプログラム「生命原理の解明を基とする医学研究教育拠点」
連絡先	iCeMS 植田グループ | ueda-g@icems.kyoto-u.ac.jp