Abstract
EDAG is multifunctional transcriptional regulator primarily expressed in the linloc-kit+Sca-1+ hematopoietic stem cells (HSC) and CD34+ progenitor cells. Previous studies indicate that EDAG is required for maintaining hematopoietic lineage commitment balance. Here using ex vivo culture and HSC transplantation models, we report that EDAG enhances the proliferative potential of human cord blood CD34+ cells, increases survival, prevents cell apoptosis and promotes their repopulating capacity. Moreover, EDAG overexpression induces rapid entry of CD34+ cells into the cell cycle. Gene expression profile analysis indicate that EDAG knockdown leads to down-regulation of various positive cell cycle regulators including cyclin A, B, D, and E. Together these data provides novel insights into EDAG in regulation of expansion and survival of human hematopoietic stem/progenitor cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD34 / metabolism*
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Apoptosis / physiology
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Cell Cycle / physiology
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Cell Proliferation / physiology*
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Cell Survival / physiology*
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Cells, Cultured
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Cord Blood Stem Cell Transplantation
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Cyclins / metabolism
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Female
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Fetal Blood / cytology
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Fetal Blood / metabolism*
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Hematopoietic Stem Cells / chemistry
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Hematopoietic Stem Cells / metabolism*
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Humans
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Interleukin Receptor Common gamma Subunit / deficiency
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Interleukin Receptor Common gamma Subunit / genetics
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Mice, Inbred NOD
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Mice, Knockout
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Mice, SCID
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
Substances
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Antigens, CD34
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Cyclins
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HEMGN protein, human
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Il2rg protein, mouse
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Interleukin Receptor Common gamma Subunit
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Nuclear Proteins
Grants and funding
This work was supported by Chinese National Natural Science Foundation Projects (81222005, 81070435); and Major State Basic Research of China (2014CBA02001, 2013CB910800).