TY - JOUR
T1 - The Transcription Factor EGR1 Controls Both the Proliferation and Localization of Hematopoietic Stem Cells
AU - Min, Irene M.
AU - Pietramaggiori, Giorgio
AU - Kim, Francis S.
AU - Passegué, Emmanuelle
AU - Stevenson, Kristen E.
AU - Wagers, Amy J.
N1 - Funding Information:
We thank Joyce LaVecchio and Girijesh Buruzula at JDC/HSCI Flow Cytometry Core for excellent cell sorting and flow cytometry analysis; Donna Neuberg (Department of Biostatistics and Computational Biology, Dana-Farber/Harvard Cancer Center) for help with statistical analysis; S. Mayack, T. Serwold, and H. Hock for critically reviewing the manuscript; and D. Williams for advice on adhesion assays. This work was supported in part by a Burroughs Wellcome Fund career award (A.J.W.), Smith Family new investigator award (A.J.W.), and NIH/NIDDK training grant T32 DK07260-30 (I.M.M.).
PY - 2008/4/10
Y1 - 2008/4/10
N2 - EGR1 is a member of the immediate early response transcription factor family and functions in cell growth, development, and stress responses in many tissues. Here we report an additional role for EGR1 in regulating homeostasis of hematopoietic stem cells (HSCs). HSCs normally express Egr1 at high levels, but dramatically downregulate its expression when induced to divide and migrate. Consistent with this finding, mice lacking Egr1 exhibit significant increases in steady-state levels of dividing HSCs in the bone marrow (BM), and a striking spontaneous mobilization of HSCs into the peripheral blood. These data identify EGR1 as a transcriptional regulator of stem cell migration that normally functions to promote HSC quiescence and retention in the niche. The ability of this single factor to regulate both proliferation and mobilization of HSCs suggests that EGR1 commands a genetic program that coordinates stem cell division and migration to maintain appropriate HSC number and function.
AB - EGR1 is a member of the immediate early response transcription factor family and functions in cell growth, development, and stress responses in many tissues. Here we report an additional role for EGR1 in regulating homeostasis of hematopoietic stem cells (HSCs). HSCs normally express Egr1 at high levels, but dramatically downregulate its expression when induced to divide and migrate. Consistent with this finding, mice lacking Egr1 exhibit significant increases in steady-state levels of dividing HSCs in the bone marrow (BM), and a striking spontaneous mobilization of HSCs into the peripheral blood. These data identify EGR1 as a transcriptional regulator of stem cell migration that normally functions to promote HSC quiescence and retention in the niche. The ability of this single factor to regulate both proliferation and mobilization of HSCs suggests that EGR1 commands a genetic program that coordinates stem cell division and migration to maintain appropriate HSC number and function.
KW - STEMCELL
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U2 - 10.1016/j.stem.2008.01.015
DO - 10.1016/j.stem.2008.01.015
M3 - Article
C2 - 18397757
AN - SCOPUS:41449118699
SN - 1934-5909
VL - 2
SP - 380
EP - 391
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 4
ER -