[PDF][PDF] Development of the fetal bone marrow niche and regulation of HSC quiescence and homing ability by emerging osteolineage cells
S Coşkun, H Chao, H Vasavada, K Heydari… - Cell reports, 2014 - cell.com
S Coşkun, H Chao, H Vasavada, K Heydari, N Gonzales, X Zhou, B de Crombrugghe…
Cell reports, 2014•cell.comHematopoietic 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 …
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 …
Summary
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.
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