Development of the fetal bone marrow niche and regulation of HSC quiescence and homing ability by emerging osteolineage cells

Cell Rep. 2014 Oct 23;9(2):581-90. doi: 10.1016/j.celrep.2014.09.013. Epub 2014 Oct 9.

Abstract

Hematopoietic stem cells (HSCs) reside within a specialized niche where interactions with vasculature, osteoblasts, and stromal components regulate their self-renewal and differentiation. Little is known about bone marrow niche formation or the role of its cellular components in HSC development; therefore, we established the timing of murine fetal long bone vascularization and ossification relative to the onset of HSC activity. Adult-repopulating HSCs emerged at embryonic day 16.5 (E16.5), coincident with marrow vascularization, and were contained within the c-Kit(+)Sca-1(+)Lin(-) (KSL) population. We used Osterix-null (Osx(-/-)) mice that form vascularized marrow but lack osteolineage cells to dissect the role(s) of these cellular components in HSC development. Osx(-/-) fetal bone marrow cells formed multilineage colonies in vitro but were hyperproliferative and failed to home to and/or engraft transplant recipients. Thus, in developing bone marrow, the vasculature can sustain multilineage progenitors, but interactions with osteolineage cells are needed to regulate long-term HSC proliferation and potential.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bone Marrow / blood supply
  • Bone Marrow / embryology*
  • Cell Lineage
  • Cell Proliferation
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism
  • Embryonic Stem Cells / physiology
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / physiology
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic
  • Osteogenesis*
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / metabolism
  • Sp7 Transcription Factor
  • Stem Cell Niche*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Sp7 Transcription Factor
  • Sp7 protein, mouse
  • Transcription Factors
  • Proto-Oncogene Proteins c-kit