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Open AccessArticle

Osteopontin is An Important Regulative Component of the Fetal Bone Marrow Hematopoietic Stem Cell Niche

1
Biomedical Manufacturing Commonwealth Scientific and Industrial Research Organisation (CSIRO), Clayton, VIC 3800, Australia
2
Australian Regenerative Medicine Institute, Monash University, Clayton, VIC 3800, Australia
3
St. Vincent’s Institute of Medical Research, Fitzroy, VIC 3065, Australia
4
The University of Melbourne, Department of Medicine at St. Vincent’s Hospital, Fitzroy, VIC 3065, Australia
*
Author to whom correspondence should be addressed.
Cells 2019, 8(9), 985; https://doi.org/10.3390/cells8090985
Received: 31 May 2019 / Revised: 1 August 2019 / Accepted: 22 August 2019 / Published: 27 August 2019
(This article belongs to the Special Issue Adding New Pieces in the Osteopontin Puzzle)
Osteopontin (OPN) is an important component in both bone and blood regulation, functioning as a bridge between the two. Previously, thrombin-cleaved osteopontin (trOPN), the dominant form of OPN in adult bone marrow (BM), was demonstrated to be a critical negative regulator of adult hematopoietic stem cells (HSC) via interactions with α4β1 and α9β1 integrins. We now demonstrate OPN is also required for fetal hematopoiesis in maintaining the HSC and progenitor pool in fetal BM. Specifically, we showed that trOPN is highly expressed in fetal BM and its receptors, α4β1 and α9β1 integrins, are both highly expressed and endogenously activated on fetal BM HSC and progenitors. Notably, the endogenous activation of integrins expressed by HSC was attributed to high concentrations of three divalent metal cations, Ca2+, Mg2+ and Mn2+, which were highly prevalent in developing fetal BM. In contrast, minimal levels of OPN were detected in fetal liver, and α4β1 and α9β1 integrins expressed by fetal liver HSC were not in the activated state, thereby permitting the massive expansion of HSC and progenitors required during early fetal hematopoiesis. Consistent with these results, no differences in the number or composition of hematopoietic cells in the liver of fetal OPN-/- mice were detected, but significant increases in the hematopoietic progenitor pool in fetal BM as well as an increase in the BM HSC pool following birth and into adulthood were observed. Together, the data demonstrates OPN is a necessary negative regulator of fetal and neonatal BM progenitors and HSC, and it exhibits preserved regulatory roles during early development, adulthood and ageing. View Full-Text
Keywords: osteopontin; fetal; hematopoietic stem cells; secreted phosphoprotein 1 osteopontin; fetal; hematopoietic stem cells; secreted phosphoprotein 1
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Cao, H.; Cao, B.; Heazlewood, C.K.; Domingues, M.; Sun, X.; Debele, E.; McGregor, N.E.; Sims, N.A.; Heazlewood, S.Y.; Nilsson, S.K. Osteopontin is An Important Regulative Component of the Fetal Bone Marrow Hematopoietic Stem Cell Niche. Cells 2019, 8, 985.

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