CD82/KAI1 Maintains the Dormancy of Long-Term Hematopoietic Stem Cells through Interaction with DARC-Expressing Macrophages

Jin Hur, Jae Il Choi, Hwan Lee, Pniel Nham, Tae Won Kim, Cheong Whan Chae, Ji Yeon Yun, Jin A. Kang, Jeehoon Kang, Sang Eun Lee, Chang Hwan Yoon, Kyungjin Boo, Seokjin Ham, Tae Young Roh, Jong Kwan Jun, Ho Lee, Sung Hee Baek, Hyo Soo Kim

Research output: Contribution to journalArticlepeer-review

117 Scopus citations

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.

Original languageEnglish
Pages (from-to)508-521
Number of pages14
JournalCell Stem Cell
Volume18
Issue number4
DOIs
StatePublished - 7 Apr 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Inc.

Keywords

  • CD82/KAI1
  • DARC/CD234
  • LT-HSCs
  • bone marrow
  • macrophage
  • quiescence
  • stem cell niche
  • tetraspanin

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