TY - JOUR
T1 - Nfix is a novel regulator of murine hematopoietic stem and progenitor cell survival
AU - Holmfeldt, Per
AU - Pardieck, Jennifer
AU - Saulsberry, Anjelica C.
AU - Nandakumar, Satish Kumar
AU - Finkelstein, David
AU - Gray, John T.
AU - Persons, Derek A.
AU - McKinney-Freeman, Shannon
N1 - Funding Information:
The authors thank Melanie Lloyd and John Morris of the Hartwell Center at St. Jude Children’s Research Hospital for assistance with gene expression arrays, Sandy Schwemberger and Richard Ashmun of the St. Jude Children’s Research Hospital Flow Cytometry Core for their expertise in cell sorting and flow cytometry, and Richard Gronostajski for Nfixfl/fl mice. This work was supported by grants from, the American Society of Hematology (K01DK080846) (S.M.-F.) and the American Lebanese Syrian Associated Charities (R03DK093731) (S.M.-F.).
Funding Information:
This work was supported by grants from, the American Society of Hematology (K01DK080846) (S.M.-F.) and the American Lebanese Syrian Associated Charities (R03DK093731) (S.M.-F.).
Publisher Copyright:
© 2013 by The American Society of Hematology.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2013-04-493973
DO - 10.1182/blood-2013-04-493973
M3 - Article
C2 - 24041575
AN - SCOPUS:84891691316
SN - 0006-4971
VL - 122
SP - 2987
EP - 2996
JO - Blood
JF - Blood
IS - 17
ER -