Impairment of Granulo-Monocytic Development of Human Common Myeloid Progenitors (CMP) but not of Granulo-Monocytic Progenitors (GMP) by Decreasing SCL/TAL1 Expression

¹ Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France.; Inserm, U567, Paris, France.

^* To whom correspondence should be addressed. E-mail: philippe.brunet-de-la-grange{at}cea.fr.

	Abstract

We recently showed that SCL/TAL1 (Stem Cell Leukemia/T-cell Acute Leukemia 1; hereafter called TAL1) regulates hematopoiesis from hematopoietic stem cells (HSC) to committed myeloid progenitors compartment. However, in this heterogeneous compartment the precise role of TAL1, that is largely debated, remains to be clearly defined notably at the Common Myeloid Progenitor (CMP) and Ganulo Monocytic Progenitor (GMP) level. Using shRNA lentiviral constructs, we decreased TAL1 expression in sorted human CMP and GMP sub-populations that were then assayed for erythroid and Granulo-Monocytic (GM) differentiation. Decreased TAL1 expression in CMP resulted in rare erythroid colonies, in a 2-3 fold reduction of GM colony number in clonogenic assays and in a 3.6 to 5.6 decreased production of CD14⁺CD15⁺ GM cells in liquid culture. Moreover, analysis of transcript profile of gene involved in GM differentiation showed that GM cells expressing shRNA-TAL1 construct displayed decreased levels of g-csfr, c/ebp, mpo and high levels of gata-2 transcripts indicating a blocking of GM differentiation. In contrast, GM differentiation of GMP remained unaffected when TAL1 transcript levels were decreased. These data definitively delineate the human myeloid progenitors that are regulated by TAL1.