Children are not little adults: just ask their hematopoietic stem cells
David A. Williams, Haiming Xu, Jose A. Cancelas
David A. Williams, Haiming Xu, Jose A. Cancelas
View: Text | PDF
Commentary

Children are not little adults: just ask their hematopoietic stem cells

Abstract

HSCs differ during ontogeny in some important parameters, including anatomic site of residence and cell cycling characteristics. In this issue of the JCI, Bowie et al. show that postnatal HSCs as well as fetal liver HSCs in mice are active in the cell cycle at much higher rates than that of adult HSCs; however, this increased frequency of cycling abruptly ceases 4 weeks after birth (see the related article beginning on page 2808). The cycling postnatal HSCs expressed high levels of CXC chemokine ligand 12 (CXCL12, also known as stromal cell–derived factor 1 [SDF-1]), a chemokine previously implicated in stem cell trafficking to the marrow cavity and shown to be expressed by cells within the hematopoietic microenvironment. These cells also possessed an engraftment defect impeding reconstitution in irradiated recipient mice, which was reversible by pretransplant administration of antagonists of the CXCL12 receptor, CXCR4. Such agents are currently clinically available, suggesting that this approach could be used to improve stem cell transplantation and engraftment.

Authors

David A. Williams, Haiming Xu, Jose A. Cancelas

×

Figure 1

Content and engraftment ability of cycling HSCs derived from fetal liver and postnatal or adult bone marrow.

Options: View larger image (or click on image) Download as PowerPoint
Content and engraftment ability of cycling HSCs derived from fetal liver...
(A) Fetal liver is enriched in G1/S/G2/M (cycling) HSCs. Fetal liver HSCs in the G1 phase are able to repopulate (blue background) syngeneic mice in a competitive repopulation assay. However, S/G2/M HSCs have lost their repopulation potential (pink background). (B) HSC content of postnatal bone marrow is reduced compared with that of fetal liver, mostly due to a reduced G1 fraction, although most HSCs are in G1 phase. At the same time, postnatal bone marrow contains a higher frequency of G0 repopulating HSCs compared with fetal liver. (C) Most bone marrow–derived HSCs are in either G0 or G1 phase. The ability of HSCs in G1 phase to engraft to irradiated recipients is lost in adult bone marrow. (D) Administration of the CXCL12/CXCR4 antagonist SDF-1G2 into recipient mice prior to transplantation enables S/G2/M HSCs from fetal liver, postnatal bone marrow, and possibly (question mark) adult bone marrow to engraft in recipient mice.