TY - JOUR
T1 - Development of the fetal bone marrow niche and regulation of HSC quiescence and homing ability by emerging osteolineage cells
AU - Coşxkun, Süleyman
AU - Chao, Hsu
AU - Vasavada, Hema
AU - Heydari, Kartoosh
AU - Gonzales, Naomi
AU - Zhou, Xin
AU - de Crombrugghe, Benoit
AU - Hirschi, Karen K.
N1 - Funding Information:
The authors thank Chris Threeton, Joel Sederstrom, and Amanda White for help with flow cytometry and Brittney Gibbons for suggestions during manuscript preparation. These studies were supported by NIH R01 grants HL077675, HL096360, and EB005173 to K.K.H.
Publisher Copyright:
© 2014 The Authors.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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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U2 - 10.1016/j.celrep.2014.09.013
DO - 10.1016/j.celrep.2014.09.013
M3 - Article
C2 - 25310984
AN - SCOPUS:84919873175
SN - 2211-1247
VL - 9
SP - 581
EP - 590
JO - Cell Reports
JF - Cell Reports
IS - 2
ER -