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Cited by 1,371

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance

Open access
Greenbaum, Adam, Hsu, Yen-Michael S., Day, Ryan B., Schuettpelz, Laura G., Christopher, Matthew J., Borgerding, Joshua N., Nagasawa, Takashi, Link, Daniel C.·2013·Nature
DOI 10.1038/nature11926
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Abstract

Haematopoietic stem cells (HSCs) primarily reside in the bone marrow where signals generated by stromal cells regulate their self-renewal, proliferation and trafficking. Endosteal osteoblasts and perivascular stromal cells including endothelial cells, CXCL12-abundant reticular cells, leptin-receptor-positive stromal cells, and nestin–green fluorescent protein (GFP)-positive mesenchymal progenitors have all been implicated in HSC maintenance. However, it is unclear whether specific haematopoietic progenitor cell (HPC) subsets reside in distinct niches defined by the surrounding stromal cells and the regulatory molecules they produce. CXCL12 (chemokine (C–X–C motif) ligand 12) regulates both HSCs and lymphoid progenitors and is expressed by all of these stromal cell populations. Here we selectively deleted Cxcl12 from candidate niche stromal cell populations and characterized the effect on HPCs. Deletion of Cxcl12 from mineralizing osteoblasts has no effect on HSCs or lymphoid progenitors. Deletion of Cxcl12 from osterix-expressing stromal cells, which include CXCL12-abundant reticular cells and osteoblasts, results in constitutive HPC mobilization and a loss of B-lymphoid progenitors, but HSC function is normal. Cxcl12 deletion from endothelial cells results in a modest loss of long-term repopulating activity. Strikingly, deletion of Cxcl12 from nestin-negative mesenchymal progenitors using Prx1–cre (Prx1 also known as Prrx1) is associated with a marked loss of HSCs, long-term repopulating activity, HSC quiescence and common lymphoid progenitors. These data suggest that osterix-expressing stromal cells comprise a distinct niche that supports B-lymphoid progenitors and retains HPCs in the bone marrow, and that expression of CXCL12 from stromal cells in the perivascular region, including endothelial cells and mesenchymal progenitors, supports HSCs.

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Metadata

Authors
Greenbaum, A., Hsu, Y.-M. S., Day, R. B., Schuettpelz, L. G., Christopher, M. J., Borgerding, J. N., Nagasawa, T., & Link, D. C.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2013-02-24
Volume
495
Issue
7440
Pages
227-230
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature11926
OpenAlex
W2012056552
Cited by
1,371
References
3
FWCI
82.54
Type
journal article
Language
en
Open access
green

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