Submitted May 12, 2006
Accepted June 18, 2006
Low SCL/TAL1 expression reveals its major role in adult hematopoietic myeloid progenitors and stem cells
Philippe Brunet de la Grange, Florence Armstrong, Veronique Duval, Marie-Christine Rouyez, Nicolas Goardon, Paul-Henri Romeo, and Francoise Pflumio*
Department of Hematology, Institut Cochin, U567 INSERM, CNRS UMR 8104, Universite Paris V
* Corresponding author; email: plume{at}cochin.inserm.fr.
SCL/TAL1 plays a key role in the development of murine primitive hematopoiesis but its functions in adult definitive hematopoiesis are still unclear. Using lentiviral delivery of TAL1-directed shRNA in human hematopoietic cells, we show that decreased expression of TAL1 induced major disorders at different levels of adult hematopoietic cell development. Erythroid but also myeloid cell production in cultures was dramatically decreased in TAL1-directed shRNA expressing cells whereas lymphoid B cell development was normal. These results confirmed the role of TAL1 in the erythroid compartment and show for the first time its implication in the function of myeloid committed progenitors. Moreover long term cultures and transplantation of TAL1 directed shRNA expressing CD34+ cells into irradiated NOD-SCID mice led to dramatically low levels of human cells of all lineages including the B lymphoid lineage, strongly suggesting a role of TAL1 in the early commitment of hematopoietic stem cells (HSC) in humans. Cultures and transplantation experiments performed with mouse sca1+ cells gave identical results. Altogether, these observations definitively show that TAL1 participates in the regulation of hematopoiesis from HSC to myeloid progenitors and pinpoint TAL1 as a master protein of human and murine adult hematopoiesis.
