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 Broxmeyer, Louis Pelus, Helmut Hanenberg, Amy Zollman, Malgorzata Kamocka, Nadia Carlesso, Angelo A. Cardoso, Melissa Kacena, Edward Srour

Research output: Contribution to journalArticle

26 Citations (Scopus)

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

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Stem Cell Niche
Hematopoietic Stem Cells
Stem cells
Osteoblasts
Chimerism
Cell Communication
Bone Marrow Cells
Mental Competency
Bone
Bone Marrow
Binding Sites
Cells

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

CD166 regulates human and murine hematopoietic stem cells and the hematopoietic niche. / Chitteti, Brahmananda Reddy; Kobayashi, Michihiro; Cheng, Yinghua; Zhang, Huajia; Poteat, Bradley A.; Broxmeyer, Hal; Pelus, Louis; Hanenberg, Helmut; Zollman, Amy; Kamocka, Malgorzata; Carlesso, Nadia; Cardoso, Angelo A.; Kacena, Melissa; Srour, Edward.

In: Blood, Vol. 124, No. 4, 24.07.2014, p. 519-529.

Research output: Contribution to journalArticle

Chitteti, BR, Kobayashi, M, Cheng, Y, Zhang, H, Poteat, BA, Broxmeyer, H, Pelus, L, Hanenberg, H, Zollman, A, Kamocka, M, Carlesso, N, Cardoso, AA, Kacena, M & Srour, E 2014, 'CD166 regulates human and murine hematopoietic stem cells and the hematopoietic niche', Blood, vol. 124, no. 4, pp. 519-529. https://doi.org/10.1182/blood-2014-03-565721
Chitteti, Brahmananda Reddy ; Kobayashi, Michihiro ; Cheng, Yinghua ; Zhang, Huajia ; Poteat, Bradley A. ; Broxmeyer, Hal ; Pelus, Louis ; Hanenberg, Helmut ; Zollman, Amy ; Kamocka, Malgorzata ; Carlesso, Nadia ; Cardoso, Angelo A. ; Kacena, Melissa ; Srour, Edward. / CD166 regulates human and murine hematopoietic stem cells and the hematopoietic niche. In: Blood. 2014 ; Vol. 124, No. 4. pp. 519-529.
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AU - Chitteti, Brahmananda Reddy

AU - Kobayashi, Michihiro

AU - Cheng, Yinghua

AU - Zhang, Huajia

AU - Poteat, Bradley A.

AU - Broxmeyer, Hal

AU - Pelus, Louis

AU - Hanenberg, Helmut

AU - Zollman, Amy

AU - Kamocka, Malgorzata

AU - Carlesso, Nadia

AU - Cardoso, Angelo A.

AU - Kacena, Melissa

AU - Srour, Edward

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