title: Nfix is a novel regulator of murine hematopoietic stem and progenitor cell survival.
abstract: Hematopoietic stem cells are both necessary and sufficient to sustain the complete blood system of vertebrates. Here we show that Nfix, a member of the nuclear factor I (Nfi) family of transcription factors, is highly expressed by hematopoietic stem and progenitor cells (HSPCs) of murine adult bone marrow. Although short hairpin RNA-mediated knockdown of Nfix expression in Lineage(-)Sca-1(+)c-Kit(+) HSPCs had no effect on in vitro cell growth or viability, Nfix-depleted HSPCs displayed a significant loss of colony-forming potential, as well as short- and long-term in vivo hematopoietic repopulating activity. Analysis of recipient mice at 4 to 20 days posttransplant revealed that Nfix-depleted HSPCs are established in the bone marrow, but fail to persist due to increased apoptotic cell death. Gene expression profiling of Nfix-depleted HSPCs reveals that loss of Nfix expression in HSPCs is concomitant with a decrease in the expression of multiple genes known to be important for HSPCs survival, such as Erg, Mecom, and Mpl. These data reveal that Nfix is a novel regulator of HSPCs survival posttransplantation and establish a role for Nfi genes in the regulation of this cellular compartment.
authors.affiliation: Department of Hematology and.
authors.forename: Per
authors.initials: P
authors.lastname: Holmfeldt
authors.forename: Jennifer
authors.initials: J
authors.lastname: Pardieck
authors.forename: Anjelica C
authors.initials: AC
authors.lastname: Saulsberry
authors.forename: Satish Kumar
authors.initials: SK
authors.lastname: Nandakumar
authors.forename: David
authors.initials: D
authors.lastname: Finkelstein
authors.forename: John T
authors.initials: JT
authors.lastname: Gray
authors.forename: Derek A
authors.initials: DA
authors.lastname: Persons
authors.forename: Shannon
authors.initials: S
authors.lastname: McKinney-Freeman
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002470:Cell Survival; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D051839:NFI Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D053628:Receptors, Thrombopoietin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG
chemical_list: D000950:Antigens, Ly; C531115:ERG protein, mouse; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; C481270:Mpl protein, mouse; D051839:NFI Transcription Factors; C497650:Nfix protein, mouse; D015513:Oncogene Proteins; D034741:RNA, Small Interfering; D053628:Receptors, Thrombopoietin; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG; D019009:Proto-Oncogene Proteins c-kit
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