PMID- 25051963 OWN - NLM STAT- MEDLINE DCOM- 20141118 LR - 20211021 IS - 1528-0020 (Electronic) IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 124 IP - 10 DP - 2014 Sep 4 TI - Gfi-1 regulates the erythroid transcription factor network through Id2 repression in murine hematopoietic progenitor cells. PG - 1586-96 LID - 10.1182/blood-2014-02-556522 [doi] AB - 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. FAU - Kim, Wonil AU - Kim W AD - Basic Science Program, Leidos Biomedical Research, Inc., Mouse Cancer and Genetics Program, Frederick National Laboratory for Cancer Research, Frederick, MD. FAU - Klarmann, Kimberly D AU - Klarmann KD AD - Basic Science Program, Leidos Biomedical Research, Inc., Mouse Cancer and Genetics Program, Frederick National Laboratory for Cancer Research, Frederick, MD. FAU - Keller, Jonathan R AU - Keller JR AD - Basic Science Program, Leidos Biomedical Research, Inc., Mouse Cancer and Genetics Program, Frederick National Laboratory for Cancer Research, Frederick, MD. LA - eng GR - HHSN261200800001C/RC/CCR NIH HHS/United States GR - HHSN261200800001E/CA/NCI NIH HHS/United States GR - ImNIH/Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural DEP - 20140722 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (DNA-Binding Proteins) RN - 0 (Gfi1 protein, mouse) RN - 0 (Idb2 protein, mouse) RN - 0 (Inhibitor of Differentiation Protein 2) RN - 0 (Transcription Factors) SB - IM EIN - Blood. 2016 Mar 17;127(11):1517 EIN - Blood. 2016 Mar 17;127(11):1517. PMID: 31265489 MH - Animals MH - Cell Differentiation/genetics MH - Cells, Cultured MH - DNA-Binding Proteins/*physiology MH - Down-Regulation/genetics MH - Erythroid Precursor Cells/physiology MH - Erythropoiesis/*genetics MH - *Gene Regulatory Networks MH - Hematopoietic Stem Cells/*metabolism MH - Inhibitor of Differentiation Protein 2/*genetics MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Transcription Factors/*genetics/metabolism/physiology PMC - PMC4155270 EDAT- 2014/07/24 06:00 MHDA- 2014/11/19 06:00 PMCR- 2015/09/04 CRDT- 2014/07/24 06:00 PHST- 2014/07/24 06:00 [entrez] PHST- 2014/07/24 06:00 [pubmed] PHST- 2014/11/19 06:00 [medline] PHST- 2015/09/04 00:00 [pmc-release] AID - S0006-4971(20)39768-8 [pii] AID - 2014/556522 [pii] AID - 10.1182/blood-2014-02-556522 [doi] PST - ppublish SO - Blood. 2014 Sep 4;124(10):1586-96. doi: 10.1182/blood-2014-02-556522. Epub 2014 Jul 22.