Hierarchical organization of osteoblasts reveals the significant role of CD166 in hematopoietic stem cell maintenance and function

Brahmananda R. Chitteti, Ying Hua Cheng, Melissa Kacena, Edward Srour

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The role of osteoblasts (OB) in maintaining hematopoietic stem cells (HSC) in their niche is well elucidated, but the exact definition, both phenotypically and hierarchically of OB responsible for these functions is not clearly known. We previously demonstrated that OB maturational status influences HSC function whereby immature OB with high Runx2 expression promote hematopoietic expansion. Here, we show that Activated Leukocyte Cell Adhesion Molecule (ALCAM) or CD166 expression on OB is directly correlated with Runx2 expression and high hematopoiesis enhancing activity (HEA). Fractionation of OB with lineage markers: Sca1, osteopontin (OPN), CD166, CD44, and CD90 revealed that Lin - Sca1 - OPN + CD166. + cells (CD166. +) and their subpopulations fractionated with CD44 and CD90 expressed high levels of Runx2 and low levels of osteocalcin (OC) demonstrating the relatively immature status of these cells. Conversely, the majority of the Lin - Sca1 - OPN + CD166 - cells (CD166 -) expressed high OC levels suggesting that CD166 - OB are more mature. In vitro hematopoietic potential of LSK cells co-cultured for 7. days with fresh OB or OB pre-cultured for 1, 2, or 3. weeks declined precipitously with increasing culture duration concomitant with loss of CD166 expression. Importantly, LSK cells co-cultured with CD166 + CD44 + CD90. + OB maintained their in vivo repopulating potential through primary and secondary transplantation, suggesting that robust HEA activity is best mediated by immature CD166. + OB with high Runx2 and low OC expression. These studies begin to define the hierarchical organization of osteoblastic cells and provide a more refined definition of OB that can mediate HEA.

Original languageEnglish
Pages (from-to)58-67
Number of pages10
JournalBone
Volume54
Issue number1
DOIs
StatePublished - May 2013

Fingerprint

Hematopoietic Stem Cells
Osteoblasts
Maintenance
Osteopontin
Osteocalcin
Hematopoiesis
Cultured Cells
Activated-Leukocyte Cell Adhesion Molecule
Transplantation

Keywords

  • CD166
  • Hematopoietic stem cells
  • Niche
  • Osteoblasts
  • Runx2

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology

Cite this

Hierarchical organization of osteoblasts reveals the significant role of CD166 in hematopoietic stem cell maintenance and function. / Chitteti, Brahmananda R.; Cheng, Ying Hua; Kacena, Melissa; Srour, Edward.

In: Bone, Vol. 54, No. 1, 05.2013, p. 58-67.

Research output: Contribution to journalArticle

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abstract = "The role of osteoblasts (OB) in maintaining hematopoietic stem cells (HSC) in their niche is well elucidated, but the exact definition, both phenotypically and hierarchically of OB responsible for these functions is not clearly known. We previously demonstrated that OB maturational status influences HSC function whereby immature OB with high Runx2 expression promote hematopoietic expansion. Here, we show that Activated Leukocyte Cell Adhesion Molecule (ALCAM) or CD166 expression on OB is directly correlated with Runx2 expression and high hematopoiesis enhancing activity (HEA). Fractionation of OB with lineage markers: Sca1, osteopontin (OPN), CD166, CD44, and CD90 revealed that Lin - Sca1 - OPN + CD166. + cells (CD166. +) and their subpopulations fractionated with CD44 and CD90 expressed high levels of Runx2 and low levels of osteocalcin (OC) demonstrating the relatively immature status of these cells. Conversely, the majority of the Lin - Sca1 - OPN + CD166 - cells (CD166 -) expressed high OC levels suggesting that CD166 - OB are more mature. In vitro hematopoietic potential of LSK cells co-cultured for 7. days with fresh OB or OB pre-cultured for 1, 2, or 3. weeks declined precipitously with increasing culture duration concomitant with loss of CD166 expression. Importantly, LSK cells co-cultured with CD166 + CD44 + CD90. + OB maintained their in vivo repopulating potential through primary and secondary transplantation, suggesting that robust HEA activity is best mediated by immature CD166. + OB with high Runx2 and low OC expression. These studies begin to define the hierarchical organization of osteoblastic cells and provide a more refined definition of OB that can mediate HEA.",
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