Nfix is a novel regulator of murine hematopoietic stem and progenitor cell survival
| Autor: | David Finkelstein, Jennifer Pardieck, Anjelica C. Saulsberry, Shannon McKinney-Freeman, Per Holmfeldt, John T. Gray, Satish K. Nandakumar, Derek A. Persons |
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| Rok vydání: | 2013 |
| Předmět: |
MECOM
Cell Survival Hematopoiesis and Stem Cells Immunology Apoptosis Bone Marrow Cells Biology Biochemistry Mice Transcriptional Regulator ERG medicine Animals Antigens Ly Progenitor cell RNA Small Interfering Oncogene Proteins Gene Expression Profiling Hematopoietic Stem Cell Transplantation Membrane Proteins Cell Biology Hematology Hematopoietic Stem Cells NFIX Molecular biology Cell biology Hematopoiesis Haematopoiesis Adult Stem Cells NFI Transcription Factors Proto-Oncogene Proteins c-kit medicine.anatomical_structure Gene Expression Regulation biology.protein Bone marrow Stem cell Receptors Thrombopoietin Adult stem cell Signal Transduction Transcription Factors |
| Zdroj: | Blood. 122(17) |
| ISSN: | 1528-0020 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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