Impact of transient down-regulation of DREAM in human embryonic stem cell pluripotency: The role of DREAM in the maintenance of hESCs

Stem Cell Res. 2016 May;16(3):568-78. doi: 10.1016/j.scr.2016.03.001. Epub 2016 Mar 4.

Abstract

Little is known about the functions of downstream regulatory element antagonist modulator (DREAM) in embryonic stem cells (ESCs). However, DREAM interacts with cAMP response element-binding protein (CREB) in a Ca(2+)-dependent manner, preventing CREB binding protein (CBP) recruitment. Furthermore, CREB and CBP are involved in maintaining ESC self-renewal and pluripotency. However, a previous knockout study revealed the protective function of DREAM depletion in brain aging degeneration and that aging is accompanied by a progressive decline in stem cells (SCs) function. Interestingly, we found that DREAM is expressed in different cell types, including human ESCs (hESCs), human adipose-derived stromal cells (hASCs), human bone marrow-derived stromal cells (hBMSCs), and human newborn foreskin fibroblasts (hFFs), and that transitory inhibition of DREAM in hESCs reduces their pluripotency, increasing differentiation. We stipulate that these changes are partly mediated by increased CREB transcriptional activity. Overall, our data indicates that DREAM acts in the regulation of hESC pluripotency and could be a target to promote or prevent differentiation in embryonic cells.

Keywords: CREB; Calsenilin; DREAM; Differentiation; Human embryonic stem cells; KChIP-3; Pluripotency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Antigens, Surface / metabolism
  • CREB-Binding Protein / genetics
  • CREB-Binding Protein / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Down-Regulation
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Human Embryonic Stem Cells / cytology
  • Human Embryonic Stem Cells / metabolism*
  • Humans
  • Kv Channel-Interacting Proteins / antagonists & inhibitors
  • Kv Channel-Interacting Proteins / genetics
  • Kv Channel-Interacting Proteins / metabolism*
  • Proteoglycans / metabolism
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Real-Time Polymerase Chain Reaction
  • Stage-Specific Embryonic Antigens / metabolism
  • Stromal Cells / cytology
  • Stromal Cells / metabolism

Substances

  • Antigens, Surface
  • Cyclic AMP Response Element-Binding Protein
  • Kv Channel-Interacting Proteins
  • Proteoglycans
  • RNA, Small Interfering
  • Stage-Specific Embryonic Antigens
  • TRA-1-60 antigen, human
  • stage-specific embryonic antigen-4
  • CREB-Binding Protein
  • CREBBP protein, human