title: CD166 regulates human and murine hematopoietic 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 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 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.
authors.affiliation: Medicine/Division of Hematology-Oncology;
authors.forename: Brahmananda Reddy
authors.initials: BR
authors.lastname: Chitteti
authors.affiliation: Pediatrics/Herman B. Wells Center for Pediatric Research;
authors.forename: Michihiro
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Orthopaedic Surgery.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Pediatrics/Herman B. Wells Center for Pediatric Research;
authors.forename: Huajia
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Medicine/Division of Hematology-Oncology;
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Poteat
authors.affiliation: Microbiology and Immunology;
authors.forename: Hal E
authors.initials: HE
authors.lastname: Broxmeyer
authors.affiliation: Microbiology and Immunology;
authors.forename: Louis M
authors.initials: LM
authors.lastname: Pelus
authors.affiliation: Pediatrics/Herman B. Wells Center for Pediatric Research;
authors.forename: Helmut
authors.initials: H
authors.lastname: Hanenberg
authors.affiliation: Pediatrics/Herman B. Wells Center for Pediatric Research;
authors.forename: Amy
authors.initials: A
authors.lastname: Zollman
authors.affiliation: Medicine/Division of Nephrology; and.
authors.forename: Malgorzata M
authors.initials: MM
authors.lastname: Kamocka
authors.affiliation: Pediatrics/Herman B. Wells Center for Pediatric Research;
authors.forename: Nadia
authors.initials: N
authors.lastname: Carlesso
authors.affiliation: Medicine/Division of Hematology-Oncology;
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Cardoso
authors.affiliation: Orthopaedic Surgery, Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Kacena
authors.affiliation: Medicine/Division of Hematology-Oncology; Pediatrics/Herman B. Wells Center for Pediatric Research; Microbiology and Immunology;
authors.forename: Edward F
authors.initials: EF
authors.lastname: Srour
mesh_terms: D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011956:Receptors, Cell Surface / Q000378:metabolism; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D055153:Stem Cell Niche / Q000502:physiology*
chemical_list: D020410:Activated-Leukocyte Cell Adhesion Molecule; D015703:Antigens, CD; D015415:Biomarkers; D011956:Receptors, Cell Surface; C000604059:SLAMF1 protein, human; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
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