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Stem Cells

A population of very small embryonic-like (VSEL) CXCR4+SSEA-1+Oct-4+ stem cells identified in adult bone marrow

Abstract

By employing multiparameter sorting, we identified in murine bone marrow (BM) a homogenous population of rare (0.02% of BMMNC) Sca-1+linCD45 cells that express by RQ-PCR and immunohistochemistry markers of pluripotent stem cells (PSC) such as SSEA-1, Oct-4, Nanog and Rex-1. The direct electronmicroscopical analysis revealed that these cells are small (2–4 μm), posses large nuclei surrounded by a narrow rim of cytoplasm, and contain open-type chromatin (euchromatin) that is typical for embryonic stem cells. In vitro cultures these cells are able to differentiate into all three germ-layer lineages. The number of these cells is highest in BM from young (1-month-old) mice and decreases with age. It is also significantly diminished in short living DBA/2J mice as compared to long living B6 animals. These cells in vitro respond strongly to SDF-1, HGF/SF and LIF and express CXCR4, c-met and LIF-R, respectively, and since they adhere to fibroblasts they may be coisolated with BM adherent cells. We hypothesize that this population of Sca-1+linCD45 very small embryonic-like (VSEL) stem cells is deposited early during development in BM and could be a source of pluripotent stem cells for tissue/organ regeneration.

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Acknowledgements

This work was supported by an NIH Grant R01 CA106281-01 and KLCRP Grant to MZR. The authors thank Chris Worth from JGB Cancer Center and Sue Rice from cytometry facility at Indiana University for help with sorting cells. The technical help of Cathie Caple for preparing TEM analysis is also appreciated.

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Correspondence to M Z Ratajczak.

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Kucia, M., Reca, R., Campbell, F. et al. A population of very small embryonic-like (VSEL) CXCR4+SSEA-1+Oct-4+ stem cells identified in adult bone marrow. Leukemia 20, 857–869 (2006). https://doi.org/10.1038/sj.leu.2404171

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  • DOI: https://doi.org/10.1038/sj.leu.2404171

Keywords

  • stem cell plasticity
  • embryonic stem cells
  • CXCR4
  • SSEA
  • Oct-4
  • SDF-1

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