Nfix is a novel regulator of murine hematopoietic stem and progenitor cell survival

Per Holmfeldt, Jennifer Pardieck, Anjelica C. Saulsberry, Satish Kumar Nandakumar, David Finkelstein, John T. Gray, Derek A. Persons, Shannon McKinney-Freeman

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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-11c-Kit1 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.

Original languageEnglish (US)
Pages (from-to)2987-2996
Number of pages10
JournalBlood
Volume122
Issue number17
DOIs
StatePublished - 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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