Abstract
Class I homeobox (HOX) genes comprise a large family of transcription factors that have been implicated in normal and malignant hematopoiesis. However, data on their expression or function during T-cell development is limited. Using degenerated RT-PCR and Affymetrix microarray analysis, we analyzed the expression pattern of this gene family in human multipotent stem cells from fetal liver (FL) and adult bone marrow (ABM), and in T-cell progenitors from child thymus. We show that FL and ABM stem cells are similar in terms of HOX gene expression, but significant differences were observed between these two cell types and child thymocytes. As the most immature thymocytes are derived from immigrated FL and ABM stem cells, this indicates a drastic change in HOX gene expression upon entry into the thymus. Further analysis of HOX-A7, HOX-A9, HOX-A10, and HOX-A11 expression with specific RT-PCR in all thymocyte differentiation stages showed a sequential loss of 3′ region HOX-A cluster genes during intrathymic T-cell development and an unexpected expression of HOX-A11, previously not recognized to play a role in hematopoiesis. Also HOX-B3 and HOX-C4 were expressed throughout thymocyte development. Overall, these data provide novel evidence for an important role of certain HOX genes in human T-cell development.
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Acknowledgements
We thank Christine Brunaud, Mario Vaneechoutte, Chris Verhofstede and Thierry De Baere for their excellent scientific advice, and Ilse Swennen, Leentje Van Simaey, Nancy De Cabooter and José De Bosscher for their technical assistance. This work was supported by grants from Ghent University, Belgium; the Flanders Institute for Biotechnology (VIB), Belgium; and the Fund for Scientific Research Flanders (FWO-Vlaanderen), Belgium.
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Taghon, T., Thys, K., De Smedt, M. et al. Homeobox gene expression profile in human hematopoietic multipotent stem cells and T-cell progenitors: implications for human T-cell development. Leukemia 17, 1157–1163 (2003). https://doi.org/10.1038/sj.leu.2402947
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DOI: https://doi.org/10.1038/sj.leu.2402947
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