title: Gfi-1 regulates the erythroid transcription factor network through Id2 repression in murine hematopoietic progenitor cells.
abstract: Growth factor independence 1 (Gfi-1) is a part of the transcriptional network that regulates the development of adult hematopoietic stem and progenitor cells. Gfi-1-null (Gfi-1(-/-)) mice have reduced numbers of hematopoietic stem cells (HSCs), impaired radioprotective function of hematopoietic progenitor cells (HPCs), and myeloid and erythroid hyperplasia. We found that the development of HPCs and erythropoiesis, but not HSC function, was rescued by reducing the expression of inhibitor of DNA-binding protein 2 (Id2) in Gfi-1(-/-) mice. Analysis of Gfi-1(-/-);Id2(+/-) mice revealed that short-term HSCs, common myeloid progenitors (CMPs), erythroid burst-forming units, colony-forming units in spleen, and more differentiated red cells were partially restored by reducing Id2 levels in Gfi-1(-/-) mice. Moreover, short-term reconstituting cells, and, to a greater extent, CMP and megakaryocyte-erythroid progenitor development, and red blood cell production (anemia) were rescued in mice transplanted with Gfi-1(-/-);Id2(+/-) bone marrow cells (BMCs) in comparison with Gfi-1(-/-) BMCs. Reduction of Id2 expression in Gfi-1(-/-) mice increased the expression of Gata1, Eklf, and EpoR, which are required for proper erythropoiesis. Reducing the levels of other Id family members (Id1 and Id3) in Gfi-1(-/-) mice did not rescue impaired HPC function or erythropoiesis. These data provide new evidence that Gfi-1 is linked to the erythroid gene regulatory network by repressing Id2 expression.
authors: Basic Science Program, Leidos Biomedical Research, Inc., Mouse Cancer and Genetics Program, Frederick National Laboratory for Cancer Research, Frederick, MD.
authors: Wonil
authors: W
authors: Kim
authors: Basic Science Program, Leidos Biomedical Research, Inc., Mouse Cancer and Genetics Program, Frederick National Laboratory for Cancer Research, Frederick, MD.
authors: Kimberly D
authors: KD
authors: Klarmann
authors: Basic Science Program, Leidos Biomedical Research, Inc., Mouse Cancer and Genetics Program, Frederick National Laboratory for Cancer Research, Frederick, MD.
authors: Jonathan R
authors: JR
authors: Keller
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology*; D015536:Down-Regulation / Q000235:genetics; D015672:Erythroid Precursor Cells / Q000502:physiology; D004920:Erythropoiesis / Q000235:genetics*; D053263:Gene Regulatory Networks; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; C079873:Gfi1 protein, mouse; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D014157:Transcription Factors