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

Brahmananda Reddy Chitteti, Michihiro Kobayashi, Yinghua Cheng, Huajia Zhang, Bradley A. Poteat, Hal E. Broxmeyer, Louis M. Pelus, Helmut Hanenberg, Amy Zollman, Malgorzata M. Kamocka, Nadia Carlesso, Angelo A. Cardoso, Melissa A. Kacena, Edward F. Srour

Research output: Contribution to journalArticle

30 Scopus citations

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 LSKCD48-CD166+CD150 + and LSKCD48-CD166+CD150+CD9 + cells, as well as human Lin-CD34+CD38 -CD49f+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 inHSCcompetence. 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 bemodulated to enhance HSC function.

Original languageEnglish (US)
Pages (from-to)519-529
Number of pages11
JournalBlood
Volume124
Issue number4
DOIs
StatePublished - Jul 24 2014

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Chitteti, B. R., Kobayashi, M., Cheng, Y., Zhang, H., Poteat, B. A., Broxmeyer, H. E., Pelus, L. M., Hanenberg, H., Zollman, A., Kamocka, M. M., Carlesso, N., Cardoso, A. A., Kacena, M. A., & Srour, E. F. (2014). CD166 regulates human and murine hematopoietic stem cells and the hematopoietic niche. Blood, 124(4), 519-529. https://doi.org/10.1182/blood-2014-03-565721