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CCCTC-binding factor is essential to the maintenance and quiescence of hematopoietic stem cells in mice

Authors
 Tae-Gyun Kim  ;  1  ;  2  ;  3  ;  4 Sueun Kim  ;  1  ;  2  ;  4 Soyeon Jung  ;  1 Mikyoung Kim  ;  1 Bobae Yang  ;  1  ;  2 Min-Geol Lee  ;  2  ;  3 and Hyoung-Pyo Kim1 
Citation
 EXPERIMENTAL AND MOLECULAR MEDICINE, Vol.49(8) : e371, 2017 
Journal Title
 EXPERIMENTAL AND MOLECULAR MEDICINE 
ISSN
 1226-3613 
Issue Date
2017
Abstract
Hematopoiesis involves a series of lineage differentiation programs initiated in hematopoietic stem cells (HSCs) found in bone marrow (BM). To ensure lifelong hematopoiesis, various molecular mechanisms are needed to maintain the HSC pool. CCCTC-binding factor (CTCF) is a DNA-binding, zinc-finger protein that regulates the expression of its target gene by organizing higher order chromatin structures. Currently, the role of CTCF in controlling HSC homeostasis is unknown. Using a tamoxifen-inducible CTCF conditional knockout mouse system, we aimed to determine whether CTCF regulates the homeostatic maintenance of HSCs. In adult mice, acute systemic CTCF ablation led to severe BM failure and the rapid shrinkage of multiple c-Kithi progenitor populations, including Sca-1+ HSCs. Similarly, hematopoietic system-confined CTCF depletion caused an acute loss of HSCs and highly increased mortality. Mixed BM chimeras reconstituted with supporting BM demonstrated that CTCF deficiency-mediated HSC depletion has both cell-extrinsic and cell-intrinsic effects. Although c-Kithi myeloid progenitor cell populations were severely reduced after ablating Ctcf, c-Kitint common lymphoid progenitors and their progenies were less affected by the lack of CTCF. Whole-transcriptome microarray and cell cycle analyses indicated that CTCF deficiency results in the enhanced expression of the cell cycle-promoting program, and that CTCF-depleted HSCs express higher levels of reactive oxygen species (ROS). Importantly, in vivo treatment with an antioxidant partially rescued c-Kithi cell populations and their quiescence. Altogether, our results suggest that CTCF is indispensable for maintaining adult HSC pools, likely by regulating ROS-dependent HSC quiescence.
Files in This Item:
T201702921.pdf Download
DOI
10.1038/emm.2017.124
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Environmental Medical Biology (환경의생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Tae-Gyun(김태균) ORCID logo https://orcid.org/0000-0002-2116-4579
Kim, Hyoung Pyo(김형표) ORCID logo https://orcid.org/0000-0003-1441-8822
Lee, Min Geol(이민걸) ORCID logo https://orcid.org/0000-0001-7040-5335
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/160636
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