STAT3-dependent long non-coding RNA Lncenc1 contributes to mouse ES cells pluripotency via stabilizing Klf4 mRNA

Brief Funct Genomics. 2024 Sep 27;23(5):651-662. doi: 10.1093/bfgp/elad045.

Abstract

Embryonic stem cells (ESCs) preserve the unique ability to differentiate into any somatic cell lineage while maintaining their self-renewal potential, relying on a complex interplay of extracellular signals regulating the expression/activity of pluripotency transcription factors and their targets. Leukemia inhibitory factor (LIF)-activated STAT3 drives ESCs' stemness by a number of mechanisms, including the transcriptional induction of pluripotency factors such as Klf4 and the maintenance of a stem-like epigenetic landscape. However, it is unknown if STAT3 directly controls stem-cell specific non-coding RNAs, crucial to balance pluripotency and differentiation. Applying a bioinformatic pipeline, here we identify Lncenc1 in mouse ESCs as an STAT3-dependent long non-coding RNA that supports pluripotency. Lncenc1 acts in the cytoplasm as a positive feedback regulator of the LIF-STAT3 axis by competing for the binding of microRNA-128 to the 3'UTR of the Klf4 core pluripotency factor mRNA, enhancing its expression. Our results unveil a novel non-coding RNA-based mechanism for LIF-STAT3-mediated pluripotency.

Keywords: Klf4; STAT3; lincRNAs; miR-128; microRNAs; naive pluripotency.

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Kruppel-Like Factor 4*
  • Kruppel-Like Transcription Factors* / genetics
  • Kruppel-Like Transcription Factors* / metabolism
  • Leukemia Inhibitory Factor* / genetics
  • Leukemia Inhibitory Factor* / metabolism
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Mouse Embryonic Stem Cells* / cytology
  • Mouse Embryonic Stem Cells* / metabolism
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism
  • RNA Stability / genetics
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • RNA, Messenger* / genetics
  • RNA, Messenger* / metabolism
  • STAT3 Transcription Factor* / genetics
  • STAT3 Transcription Factor* / metabolism

Substances

  • Kruppel-Like Factor 4
  • Klf4 protein, mouse
  • STAT3 Transcription Factor
  • RNA, Long Noncoding
  • Kruppel-Like Transcription Factors
  • RNA, Messenger
  • Leukemia Inhibitory Factor
  • Stat3 protein, mouse
  • MicroRNAs