TRIM32 modulates pluripotency entry and exit by directly regulating Oct4 stability

Lamia'a Bahnassawy, Thanneer M Perumal, Laura Gonzalez-Cano, Anna-Lena Hillje, Leila Taher, Wojciech Makalowski, Yutaka Suzuki, Georg Fuellen, Antonio del Sol, Jens Christian Schwamborn

Research output: Contribution to journalArticle

Abstract

Induced pluripotent stem cells (iPSCs) have revolutionized the world of regenerative medicine; nevertheless, the exact molecular mechanisms underlying their generation and differentiation remain elusive. Here, we investigated the role of the cell fate determinant TRIM32 in modulating such processes. TRIM32 is essential for the induction of neuronal differentiation of neural stem cells by poly-ubiquitinating cMyc to target it for degradation resulting in inhibition of cell proliferation. To elucidate the role of TRIM32 in regulating somatic cell reprogramming we analysed the capacity of TRIM32-knock-out mouse embryonic fibroblasts (MEFs) in generating iPSC colonies. TRIM32 knock-out MEFs produced a higher number of iPSC colonies indicating a role for TRIM32 in inhibiting this cellular transition. Further characterization of the generated iPSCs indicated that the TRIM32 knock-out iPSCs show perturbed differentiation kinetics. Additionally, mathematical modelling of global gene expression data revealed that during differentiation an Oct4 centred network in the wild-type cells is replaced by an E2F1 centred network in the TRIM32 deficient cells. We show here that this might be caused by a TRIM32-dependent downregulation of Oct4. In summary, the data presented here reveal that TRIM32 directly regulates at least two of the four Yamanaka Factors (cMyc and Oct4), to modulate cell fate transitions.

Original languageEnglish
Pages (from-to)13456
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - 26 Aug 2015

Keywords

  • Animals
  • Cell Differentiation/physiology
  • Cells, Cultured
  • Fibroblasts/cytology
  • Gene Expression Regulation, Developmental/physiology
  • Mice
  • Mice, Inbred C57BL
  • Octamer Transcription Factor-3/metabolism
  • Pluripotent Stem Cells/cytology
  • Ubiquitin-Protein Ligases/metabolism

Fingerprint Dive into the research topics of 'TRIM32 modulates pluripotency entry and exit by directly regulating Oct4 stability'. Together they form a unique fingerprint.

Cite this