@article{7ee210b849bb459e9bb7ad1dda41623c,
title = "CD82/KAI1 Maintains the Dormancy of Long-Term Hematopoietic Stem Cells through Interaction with DARC-Expressing Macrophages",
abstract = "Hematopoiesis is regulated by crosstalk between long-term repopulating hematopoietic stem cells (LT-HSCs) and supporting niche cells in the bone marrow (BM). Here, we examine the role of CD82/KAI1 in niche-mediated LT-HSC maintenance. We found that CD82/KAI1 is expressed predominantly on LT-HSCs and rarely on other hematopoietic stem-progenitor cells (HSPCs). In Cd82-/- mice, LT-HSCs were selectively lost as they exited from quiescence and differentiated. Mechanistically, CD82-based TGF-β1/Smad3 signaling leads to induction of CDK inhibitors and cell-cycle inhibition. The CD82 binding partner DARC/CD234 is expressed on macrophages and stabilizes CD82 on LT-HSCs, promoting their quiescence. When DARC+ BM macrophages were ablated, the level of surface CD82 on LT-HSCs decreased, leading to cell-cycle entry, proliferation, and differentiation. A similar interaction appears to be relevant for human HSPCs. Thus, CD82 is a functional surface marker of LT-HSCs that maintains quiescence through interaction with DARC-expressing macrophages in the BM stem cell niche.",
keywords = "bone marrow, CD82/KAI1, DARC/CD234, LT-HSCs, macrophage, quiescence, stem cell niche, tetraspanin",
author = "Jin Hur and Choi, {Jae Il} and Hwan Lee and Pniel Nham and Kim, {Tae Won} and Chae, {Cheong Whan} and Yun, {Ji Yeon} and Kang, {Jin A.} and Jeehoon Kang and Lee, {Sang Eun} and Yoon, {Chang Hwan} and Kyungjin Boo and Seokjin Ham and Roh, {Tae Young} and Jun, {Jong Kwan} and Ho Lee and Baek, {Sung Hee} and Kim, {Hyo Soo}",
note = "Funding Information: H.-S.K. is supported by the Bio and Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIP) (NRF-2015M3A9B4051041). H.-S.K. is also supported by the Innovative Research Institute for Cell Therapy (A062260) and Korea Health Technology R&D Project (HI14C1277) through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health and Welfare (MHW). J.H. is supported by the Bio and Medical Technology Development Program of the NRF funded by the MSIP (NRF-2015M3A9B4051198). S.H.B. is supported by a grant from the Creative Research Initiatives Program (2009-0081563) of the NRF. The authors would like to thank Prof. Je-Yeol Cho for kindly providing the C166 cell line. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = apr,
day = "7",
doi = "10.1016/j.stem.2016.01.013",
language = "English",
volume = "18",
pages = "508--521",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "4",
}