Blood Journal
Leading the way in experimental and clinical research in hematology

CD166 regulates human and murine hematopoietic stem cells and the hematopoietic niche

  1. Brahmananda Reddy Chitteti1,
  2. Michihiro Kobayashi2,
  3. Yinghua Cheng3,
  4. Huajia Zhang2,
  5. Bradley A. Poteat1,
  6. Hal E. Broxmeyer4,
  7. Louis M. Pelus4,
  8. Helmut Hanenberg2,
  9. Amy Zollman2,
  10. Malgorzata M. Kamocka5,
  11. Nadia Carlesso2,
  12. Angelo A. Cardoso1,
  13. Melissa A. Kacena3,6, and
  14. Edward F. Srour1,2,4
  1. 1Medicine/Division of Hematology-Oncology;
  2. 2Pediatrics/Herman B. Wells Center for Pediatric Research;
  3. 3Orthopaedic Surgery,
  4. 4Microbiology and Immunology;
  5. 5Medicine/Division of Nephrology; and
  6. 6Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN

Key Points

  • CD166 identifies human and murine long-term repopulating stem cells.

  • CD166 is a functional marker of stem cells and the hematopoietic niche.

Abstract

We previously showed that immature CD166+ osteoblasts (OB) promote hematopoietic stem cell (HSC) function. Here, we demonstrate that CD166 is a functional HSC marker that identifies both murine and human long-term repopulating cells. Both murine LSKCD48CD166+CD150+ and LSKCD48CD166+CD150+CD9+ cells, as well as human LinCD34+CD38CD49f+CD166+ cells sustained significantly higher levels of chimerism in primary and secondary recipients than CD166 cells. CD166−/− knockout (KO) LSK cells engrafted poorly in wild-type (WT) recipients and KO bone marrow cells failed to radioprotect lethally irradiated WT recipients. CD166−/− hosts supported short-term, but not long-term WT HSC engraftment, confirming that loss of CD166 is detrimental to the competence of the hematopoietic niche. CD166−/− mice were significantly more sensitive to hematopoietic stress. Marrow-homed transplanted WT hematopoietic cells lodged closer to the recipient endosteum than CD166−/− cells, suggesting that HSC-OB homophilic CD166 interactions are critical for HSC engraftment. STAT3 has 3 binding sites on the CD166 promoter and STAT3 inhibition reduced CD166 expression, suggesting that both CD166 and STAT3 may be functionally coupled and involved in HSC competence. These studies illustrate the significance of CD166 in the identification and engraftment of HSC and in HSC-niche interactions, and suggest that CD166 expression can be modulated to enhance HSC function.

  • Submitted March 27, 2014.
  • Accepted April 9, 2014.
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