Overexpression of a hematopoietic transcriptional regulator EDAG induces myelopoiesis and suppresses lymphopoiesis in transgenic mice.
Erythroid differentiation-associated gene (EDAG) is a hematopoietic tissue-specific gene that is highly expressed in the earliest CD34+ lin- bone marrow (BM) cells and involved in the proliferation and differentiation of hematopoietic cells. To investigate the role of EDAG in hematopoiesis, we established an EDAG transgenic mouse model driven by human CD11a promoter. The transgenic mice showed increased mortality with severe organ infiltration by neutrophils, and the homeostasis of hematopoiesis was broken. The myelopoiesis was enhanced with expansion of myeloid cells in BM, increased peripheral granulocytes and extramedullary myelopoiesis in spleen. In contrast to myeloid cells, the lymphoid commitment was severely impaired with the B lymphopoiesis blocked at the transition from pro/pre-B I to pre-B II stage in BM and T thymocytes development blocked at the most immature stage (DN I). Moreover, we showed that EDAG was a transcriptional regulator which had transactivation activity and regulated the expression of several key transcription factors such as PU.1 and Pax5 in transgenic hematopoietic stem cells. These data suggested that EDAG was a key transcriptional regulator in maintaining the homeostasis of hematopoietic lineage commitment.
Li
C-Y
CY
Department of Biochemistry and Molecular Biology, Beijing Institute of Radiation Medicine, Beijing, China.
Zhan
Y-Q
YQ
Li
W
W
Xu
C-W
CW
Xu
W-X
WX
Yu
D-H
DH
Peng
R-Y
RY
Cui
Y-F
YF
Yang
X
X
Hou
N
N
Li
Y-H
YH
Dong
B
B
Sun
H-B
HB
Yang
X-M
XM
D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis; D040881:CD11a Antigen / Q000096:biosynthesis; D002454:Cell Differentiation; D019070:Cell Lineage; D006410:Hematopoiesis; D006413:Hematopoietic System / Q000378:metabolism*; D038041:Lymphopoiesis; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D038042:Myelopoiesis; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D018952:Antigens, CD34; D040881:CD11a Antigen; C486660:Hemgn protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors