Haematopoietic stem cells retain long-term repopulating activity and multipotency in the absence of stem-cell leukaemia SCL/tal-1 gene

Hanna K. A. Mikkola, Jenny Klintman, Haidi Yang, Hanno Hock, Thorsten M. Schlaeger, Yuko Fujiwara and Stuart H. Orkin ()
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Hanna K. A. Mikkola: Harvard Medical School and Howard Hughes Medical Institute
Jenny Klintman: Harvard Medical School and Howard Hughes Medical Institute
Haidi Yang: Harvard Medical School and Howard Hughes Medical Institute
Hanno Hock: Harvard Medical School and Howard Hughes Medical Institute
Thorsten M. Schlaeger: Harvard Medical School and Howard Hughes Medical Institute
Yuko Fujiwara: Harvard Medical School and Howard Hughes Medical Institute
Stuart H. Orkin: Harvard Medical School and Howard Hughes Medical Institute

Nature, 2003, vol. 421, issue 6922, 547-551

Abstract: Abstract The production of blood cells is sustained throughout the lifetime of an individual by haematopoietic stem cells (HSCs)1. Specification of HSCs from mesoderm during embryonic development requires the stem cell leukaemia SCL/tal-1 gene product2,3,4,5,6. Forced expression of SCL/tal-1 strongly induces blood formation in embryos, indicating that this gene has a dominant role in commitment to haematopoiesis7,8. In the adult haematopoietic system, expression of SCL/tal-1 is enriched in HSCs and multipotent progenitors, and in erythroid and megakaryocytic lineages9,10,11, consistent with roles for this factor in adult haematopoiesis. Here we assess by conditional gene targeting whether SCL/tal-1 is required continuously for the identity and function of HSCs. We find that SCL/tal-1 is dispensable for HSC engraftment, self-renewal and differentiation into myeloid and lymphoid lineages; however, the proper differentiation of erythroid and megakaryocytic precursors is dependent on SCL/tal-1. Thus, SCL/tal-1 is essential for the genesis of HSCs, but its continued expression is not essential for HSC functions. These findings contrast with lineage choice mechanisms, in which the identity of haematopoietic lineages requires continuous transcription factor expression12,13.

Date: 2003
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DOI: 10.1038/nature01345

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