지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.4
- 수록면
- 43 - 55 (13page)
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Hematopoietic stem cells (HSCs) in bone marrow are pluripotent cells that can constitute the hematopoiesis system through self-renewal and differentiation into immune cells and red blood cells. To ensure a competent hematopoietic system for life, the maintenance of HSCs is tightly regulated. Although autophagy, a self-degradation pathway for cell homeostasis, is essential for hematopoiesis, the role of autophagy key protein Atg5 in HSCs has not been thoroughly investigated. In this study, we found that Atg5 deficiency in hematopoietic cells causes survival defects, resulting in severe lymphopenia and anemia in mice. In addition, the absolute numbers of HSCs and multiple-lineage progenitor cells were significantly decreased, and abnormal erythroid development resulted in reduced erythrocytes in blood of Vav_Atg5−/− mice. The proliferation of Lin−Sca-1+c-Kit+ HSCs was aberrant in bone marrow of Vav_Atg5−/−mice, and mature progenitors and terminally differentiated cells were also significantly altered. Furthermore, the reconstitution ability of HSCs in bone marrow chimeric mice was significantly decreased in the presence of Atg5 deficiency in HSCs. Mechanistically, impairment of autophagy-mediated clearance of damaged mitochondria was the underlying cause of the HSC functional defects. Taken together, these results define the crucial role of Atg5 in the maintenance and the reconstitution ability of HSCs.
목차
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
참고문헌 (35)
참고문헌 신청
Sugiyama T / 2006 / Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches / Immunity 25:977~988
Guerrouahen BS / 2011 / Osteoblastic and vascular endothelial niches, their control on normal hematopoietic stem cells, and their consequences on the development of leukemia / Stem Cells Int 2011:375857
Tipping AJ / 2009 / High GATA-2 expression inhibits human hematopoietic stem and progenitor cell function by effects on cell cycle / Blood 113:2661~2672
Park IK / 2003 / Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells / Nature 423:302~305
Iwama A / 2004 / Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1 / Immunity :843~851
Guerrouahen BS / 2011 / Osteoblastic and vascular endothelial niches, their control on normal hematopoietic stem cells, and their consequences on the development of leukemia / Stem Cells Int 2011:375857
Tipping AJ / 2009 / High GATA-2 expression inhibits human hematopoietic stem and progenitor cell function by effects on cell cycle / Blood 113:2661~2672
Park IK / 2003 / Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells / Nature 423:302~305
Iwama A / 2004 / Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1 / Immunity :843~851
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UCI(KEPA) : I410-ECN-0101-2019-517-000788724