Original Article

Leukemia (2006) 20, 857–869. doi:10.1038/sj.leu.2404171; published online 23 February 2006

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

M Kucia1, R Reca1, F R Campbell1, E Zuba-Surma1, M Majka1, J Ratajczak1 and M Z Ratajczak1

1Stem Cell Biology Program at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA

Correspondence: Professor MZ Ratajczak, Stem Cell Biology Program, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA. E-mail: mzrata01@louisville.edu

Received 29 January 2006; Accepted 10 February 2006; Published online 23 February 2006.

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Abstract

By employing multiparameter sorting, we identified in murine bone marrow (BM) a homogenous population of rare (approx0.02% of BMMNC) Sca-1+lin-CD45- 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 (approx2–4 mum), 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 (approx1-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+lin-CD45- 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.

Keywords:

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

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