The transcription factor EGR1 controls both the proliferation and localization of hematopoietic stem cells.
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.
Min
Irene M
IM
Section on Developmental and Stem Cell Biology, Joslin Diabetes Center, Boston, MA 02115, USA.
Pietramaggiori
Giorgio
G
Kim
Francis S
FS
Passegué
Emmanuelle
E
Stevenson
Kristen E
KE
Wagers
Amy J
AJ
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000502:physiology; D016026:Bone Marrow Transplantation; D002453:Cell Cycle; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002633:Chemotaxis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000502:physiology; D051766:Early Growth Response Protein 1 / Q000502:physiology*; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006413:Hematopoietic System; D051379:Mice; D008822:Mice, Transgenic; D036102:Peripheral Blood Stem Cell Transplantation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018952:Antigens, CD34; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D012333:RNA, Messenger