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Mature Let-7 miRNAs fine tune expression of LIN28B in pluripotent human embryonic stem cells

Nelly Rahkonen1, Aki Stubb1, Maia Malonzo2

  • 1Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku 20520, Finland.

Stem Cell Research
|October 25, 2016
PubMed

Insights

Human embryonic stem cells (hESC) maintain pluripotency differently than mouse ES cells (mESC). Unlike mESCs, hESCs express mature Let-7 microRNAs (miRNAs) and LIN28 proteins simultaneously, revealing novel regulatory insights.

Area of Science:

  • Stem cell biology
  • Molecular regulation of pluripotency
  • Epigenetics and gene regulation

Background:

  • MicroRNAs (miRNAs) are key regulators of biological processes, including stem cell self-renewal.
  • The Lin28-Let-7 pathway is a well-studied miRNA-protein interaction in stem cell regulation.
  • Existing models primarily focus on mouse ESCs (mESC) and cancer cells, potentially overlooking human-specific mechanisms.

Purpose of the Study:

  • To investigate the role of the Lin28-Let-7 pathway in human embryonic stem cell (hESC) pluripotency.
  • To compare the Lin28-Let-7 regulatory mechanism in hESCs with established models in mESCs and cancer cells.
  • To elucidate novel aspects of human pluripotency maintenance.

Main Methods:

  • Analysis of mature Let-7 miRNA and LIN28 protein expression in pluripotent and differentiating hESCs.
  • Investigating the regulatory relationship between mature Let-7 miRNAs and LIN28 proteins (specifically LIN28B).
  • Assessing the impact of LIN28 protein silencing on mature Let-7 miRNA levels.

Main Results:

  • Human ESCs (hESCs) express mature Let-7 family miRNAs concurrently with all LIN28 proteins, contrasting with mESC models.
  • Mature Let-7 miRNAs are differentially regulated during hESC differentiation, showing an inverse correlation with LIN28B expression.
  • Mature Let-7 miRNAs modulate LIN28B protein levels in pluripotent hESCs, but LIN28 silencing does not affect mature Let-7 levels.

Conclusions:

  • Human ESC pluripotency maintenance exhibits a distinct Lin28-Let-7 regulatory mechanism compared to mESCs.
  • The findings provide new insights into the complex regulatory network governing human pluripotency.
  • This study highlights significant differences in Lin28-Let-7 regulation between human and mouse stem cells.
Keywords:
Human embryonic stem cellLIN28Let-7Pluripotency

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