The suppression of zfpm-1 accelerates the erythropoietic differentiation of human CD34+ cells.
Erythropoiesis is a complex multistage process for the differentiation of mature erythrocytes from hematopoietic stem cells. The function of several transcription factors has been reported in hematopoietic stem cell differentiation. However, the molecular basis governing its functional behavior is unclear. In this study, we characterized the role of Zfpm-1 during the erythropoietic differentiation of human hematopoietic stem cells. To verify the function of Zfpm-1 during erythropoietic differentiation, we established human CD34+ cell culture system by using human umbilical cord blood. At day 7 of the human CD34+ cell differentiation process to proerythocytes, Zfpm-1 was initially up-regulated and then dramatically down-regulated at day 9. The Zfpm-1 siRNA transfected HSCs contained 20% more GPA+ cells than the mock transfected cells, and showed repressed expression of the hematopoietic transcription factors, c-myc and c-myb, but increased expression of GATA-1. In contrast, the Zfpm-1 gain-of-function is the opposite of loss-of-function results above.
Yang
Hee-Young
HY
Department of Molecular Medicine, Chonnam National University, Gwangju, Republic of Korea.
Kim
Sue Hee
SH
Kim
Seok-Ho
SH
Kim
Dong-Jun
DJ
Kim
Sun-Uk
SU
Yu
Dae-Yeul
DY
Yeom
Young Il
YI
Lee
Dong-Seok
DS
Kim
Yong-Jun
YJ
Park
Byung-Ju
BJ
Lee
Tae-Hoon
TH
D018952:Antigens, CD34 / Q000032:analysis*; D001483:Base Sequence; D018955:CD36 Antigens / Q000032:analysis; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D004920:Erythropoiesis / Q000235:genetics / Q000502:physiology; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism; D005434:Flow Cytometry; D050982:GATA1 Transcription Factor / Q000235:genetics; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010957:Plasmids / Q000235:genetics; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D018952:Antigens, CD34; D018955:CD36 Antigens; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; C489427:MYC protein, human; D009687:Nuclear Proteins; D020598:Proto-Oncogene Proteins c-myb; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors; C498432:ZFPM1 protein, human