Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 1,303

The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.

Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches

Open access
Ding, Lei, Morrison, Sean J.·2013·Nature
DOI 10.1038/nature11885
Open this paper in CoChat — free account

Abstract

Although haematopoietic stem cells (HSCs) are commonly assumed to reside within a specialized microenvironment, or niche, most published experimental manipulations of the HSC niche have affected the function of diverse restricted progenitors. This raises the fundamental question of whether HSCs and restricted progenitors reside within distinct, specialized niches or whether they share a common niche. Here we assess the physiological sources of the chemokine CXCL12 for HSC and restricted progenitor maintenance. Cxcl12DsRed knock-in mice (DsRed-Express2 recombined into the Cxcl12 locus) showed that Cxcl12 was primarily expressed by perivascular stromal cells and, at lower levels, by endothelial cells, osteoblasts and some haematopoietic cells. Conditional deletion of Cxcl12 from haematopoietic cells or nestin–cre-expressing cells had little or no effect on HSCs or restricted progenitors. Deletion of Cxcl12 from endothelial cells depleted HSCs but not myeloerythroid or lymphoid progenitors. Deletion of Cxcl12 from perivascular stromal cells depleted HSCs and certain restricted progenitors and mobilized these cells into circulation. Deletion of Cxcl12 from osteoblasts depleted certain early lymphoid progenitors but not HSCs or myeloerythroid progenitors, and did not mobilize these cells into circulation. Different stem and progenitor cells thus reside in distinct cellular niches in bone marrow: HSCs occupy a perivascular niche and early lymphoid progenitors occupy an endosteal niche.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/nature11885

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 4 references

Research works printed but not linked: 38

  1. Morrison, S. J. & Spradling, A. C. Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell 132, 598–611 (2008) · DOI
  2. Kondo, M., Weissman, I. L. & Akashi, K. Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 91, 661–672 (1997) · DOI · Paper page
  3. Kiel, M. J., Yilmaz, O. H., Iwashita, T., Terhorst, C. & Morrison, S. J. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 121, 1109–1121 (2005) · DOI · Paper page
  4. Morita, Y., Ema, H. & Nakauchi, H. Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment. J. Exp. Med. 207, 1173–1182 (2010) · DOI · Paper page
  5. Foudi, A. et al. Analysis of histone 2B-GFP retention reveals slowly cycling hematopoietic stem cells. Nature Biotechnol. 27, 84–90 (2009) · DOI · Paper page
  6. Kiel, M. J., Radice, G. L. & Morrison, S. J. Lack of evidence that hematopoietic stem cells depend on N-cadherin-mediated adhesion to osteoblasts for their maintenance. Cell Stem Cell 1, 204–217 (2007) · DOI · Paper page
  7. Ding, L., Saunders, T. L., Enikolopov, G. & Morrison, S. J. Endothelial and perivascular cells maintain haematopoietic stem cells. Nature 481, 457–462 (2012) · DOI
  8. Sugiyama, T., Kohara, H., Noda, M. & Nagasawa, T. Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity 25, 977–988 (2006) · DOI
  9. Mendéz-Ferrer, S. et al. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 466, 829–834 (2010) · DOI · Paper page
  10. Lo Celso, C. et al. Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche. Nature 457, 92–96 (2009) · DOI · Paper page
  11. Tzeng, Y. S. et al. Loss of Cxcl12/Sdf-1 in adult mice decreases the quiescent state of hematopoietic stem/progenitor cells and alters the pattern of hematopoietic regeneration after myelosuppression. Blood 117, 429–439 (2011) · DOI · Paper page
  12. Nagasawa, T. et al. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 382, 635–638 (1996) · DOI · Paper page
  13. Petit, I. et al. G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nature Immunol. 3, 687–694 (2002) · DOI · Paper page
  14. Ara, T. et al. Long-term hematopoietic stem cells require stromal cell-derived factor-1 for colonizing bone marrow during ontogeny. Immunity 19, 257–267 (2003) · DOI
  15. Nagasawa, T., Kikutani, H. & Kishimoto, T. Molecular cloning and structure of a pre-B-cell growth-stimulating factor. Proc. Natl Acad. Sci. USA 91, 2305–2309 (1994) · DOI · Paper page
  16. Nie, Y., Han, Y. C. & Zou, Y. R. CXCR4 is required for the quiescence of primitive hematopoietic cells. J. Exp. Med. 205, 777–783 (2008) · DOI · Paper page
  17. Ponomaryov, T. et al. Induction of the chemokine stromal-derived factor-1 following DNA damage improves human stem cell function. J. Clin. Invest. 106, 1331–1339 (2000) · DOI · Paper page
  18. Dar, A. et al. Chemokine receptor CXCR4-dependent internalization and resecretion of functional chemokine SDF-1 by bone marrow endothelial and stromal cells. Nature Immunol. 6, 1038–1046 (2005) · DOI · Paper page
  19. Kawabata, K. et al. A cell-autonomous requirement for CXCR4 in long-term lymphoid and myeloid reconstitution. Proc. Natl Acad. Sci. USA 96, 5663–5667 (1999) · DOI
  20. Liu, F. et al. Expression and activity of osteoblast-targeted Cre recombinase transgenes in murine skeletal tissues. Int. J. Dev. Biol. 48, 645–653 (2004) · DOI
  21. Adolfsson, J. et al. Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential a revised road map for adult blood lineage commitment. Cell 121, 295–306 (2005) · DOI · Paper page
  22. Inlay, M. A. et al. Ly6d marks the earliest stage of B-cell specification and identifies the branchpoint between B-cell and T-cell development. Genes Dev. 23, 2376–2381 (2009) · DOI · Paper page
  23. Logan, M. et al. Expression of Cre recombinase in the developing mouse limb bud driven by a Prxl enhancer. Genesis 33, 77–80 (2002) · DOI · Paper page
  24. Greenbaum, A. et al. CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance. Nature http://dx.doi.org/10.1038/nature11926 (2013) · DOI · Paper page
  25. Visnjic, D. et al. Hematopoiesis is severely altered in mice with an induced osteoblast deficiency. Blood 103, 3258–3264 (2004) · DOI
  26. Zhu, J. et al. Osteoblasts support B lymphocyte commitment and differentiation from hematopoietic stem cells. Blood 109, 3706–3712 (2007) · DOI
  27. Wu, J. Y. et al. Osteoblastic regulation of B lymphopoiesis is mediated by GSα-dependent signaling pathways. Proc. Natl Acad. Sci. USA 105, 16976–16981 (2008) · DOI
  28. Liu, P., Jenkins, N. A. & Copeland, N. G. A highly efficient recombineering-based method for generating conditional knockout mutations. Genome Res. 13, 476–484 (2003) · DOI · Paper page
  29. Rodriguez, C. I. et al. High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP. Nature Genet. 25, 139–140 (2000) · DOI · Paper page
  30. Ruzankina, Y. et al. Deletion of the developmentally essential gene ATR in adult mice leads to age-related phenotypes and stem cell loss. Cell Stem Cell 1, 113–126 (2007) · DOI · Paper page
  31. de Boer, J. et al. Transgenic mice with hematopoietic and lymphoid specific expression of Cre. Eur. J. Immunol. 33, 314–325 (2003) · DOI · Paper page
  32. Tronche, F. et al. Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety. Nature Genet. 23, 99–103 (1999) · DOI
  33. Koni, P. A. et al. Conditional vascular cell adhesion molecule 1 deletion in mice: impaired lymphocyte migration to bone marrow. J. Exp. Med. 193, 741–754 (2001) · DOI · Paper page
  34. DeFalco, J. et al. Virus-assisted mapping of neural inputs to a feeding center in the hypothalamus. Science 291, 2608–2613 (2001) · DOI · Paper page
  35. Srinivas, S. et al. Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus. BMC Dev. Biol. 1, 4 (2001) · DOI · Paper page
  36. Kalajzic, Z. et al. Directing the expression of a green fluorescent protein transgene in differentiated osteoblasts: comparison between rat type I collagen and rat osteocalcin promoters. Bone 31, 654–660 (2002) · DOI
  37. Butler, J. M. et al. Endothelial cells are essential for the self-renewal and repopulation of Notch-dependent hematopoietic stem cells. Cell Stem Cell 6, 251–264 (2010) · DOI · Paper page
  38. Semerad, C. L. et al. G-CSF potently inhibits osteoblast activity and CXCL12 mRNA expression in the bone marrow. Blood 106, 3020–3027 (2005) · DOI

Cited by

See all 1,303

Metadata

Authors
Ding, L., & Morrison, S. J.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2013-02-24
Volume
495
Issue
7440
Pages
231-235
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature11885
OpenAlex
W2005718040
Cited by
1,303
References
4
FWCI
78.28
Type
journal article
Language
en
Update notices
erratum (2014-10-08)
Open access
green
Licence

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches. https://app.cochat.ai/papers/10.1038/nature11885
The paper
Ding, L., & Morrison, S. J. (2013). Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches. Nature. https://doi.org/10.1038/nature11885

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.