Impairment of granulo-monocytic development of human common myeloid progenitors but not of granulo-monocytic progenitors by decreasing stem cell leukemia/T-cell acute leukemia 1 expression.
We recently showed that Stem Cell Leukemia/T-cell Acute Leukemia 1 (SCL/TAL1) regulates hematopoiesis from hematopoietic stem cells 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 granulo-monocytic progenitor (GMP) levels. Using small hairpin (sh)RNA lentiviral constructs, we decreased TAL1 expression in sorted human CMP and GMP subpopulations 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 3.6-5.6 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/ebpalpha, and 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. Disclosure of potential conflicts of interest is found at the end of this article.
Brunet de la Grange
Philippe
P
Zink
Estelle
E
Armstrong
Florence
F
Rouyez
Marie-Christine
MC
Pflumio
Françoise
F
D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D002454:Cell Differentiation; D002469:Cell Separation; D005312:Fetal Blood / Q000166:cytology; D005786:Gene Expression Regulation; D006098:Granulocytes / Q000166:cytology*; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D009000:Monocytes / Q000166:cytology*; D023461:Myeloid Progenitor Cells / Q000166:cytology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D012313:RNA / Q000235:genetics; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1
D015703:Antigens, CD; D018952:Antigens, CD34; D051792:Basic Helix-Loop-Helix Proteins; D011518:Proto-Oncogene Proteins; D012313:RNA; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; C067143:TAL1 protein, human