Abstract
Hematopoietic stem cells in the bone marrow (BM) give rise to all blood cells. According to the classic model of hematopoiesis, the differentiation paths leading to the myeloid and lymphoid lineages segregate early. A candidate ‘common lymphoid progenitor’ (CLP) has been isolated from CD34+CD38− human cord blood cells based on CD7 expression. Here, we confirm the B- and NK-differentiation potential of CD34+CD38−CD7+ cells and show in addition that this population has strong capacity to differentiate into T cells. As CD34+CD38−CD7+ cells are virtually devoid of myeloid differentiation potential, these cells represent true CLPs. To unravel the molecular mechanisms underlying lymphoid commitment, we performed genome-wide gene expression profiling on sorted CD34+CD38−CD7+ and CD34+CD38−CD7− cells. Interestingly, lymphoid-affiliated genes were mainly upregulated in the CD7+ population, while myeloid-specific genes were downregulated. This supports the hypothesis that lineage commitment is accompanied by the shutdown of inappropriate gene expression and the upregulation of lineage-specific genes. In addition, we identified several highly expressed genes that have not been described in hematopoiesis before.
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Acknowledgements
We thank the staff of the Bloedtransfusiecentrum Oost-Vlaanderen for the supply of umbilical cord blood samples and Marie-José De Bosscher for lymphoprepping. We are grateful to Dick De Ridder for help with microarray analysis and to Inge Van de Walle for excellent technical assistance. This work was supported by grants from the Fund for Scientific Research Flanders (Belgium) and from the Ghent University concerted research program.
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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)
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Hoebeke, I., De Smedt, M., Stolz, F. et al. T-, B- and NK-lymphoid, but not myeloid cells arise from human CD34+CD38−CD7+ common lymphoid progenitors expressing lymphoid-specific genes. Leukemia 21, 311–319 (2007). https://doi.org/10.1038/sj.leu.2404488
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DOI: https://doi.org/10.1038/sj.leu.2404488
Keywords
- human
- hematopoiesis
- stem cells
- cord blood
- lymphoid progenitor
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