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Permissiveness to form pluripotent stem cells may be an evolutionarily derived characteristic in Mus musculus

Tiffany A Garbutt1, Thomas I Konneker1, Kranti Konganti2,3

  • 1Program in Genetics, Department of Biological Science, North Carolina State University, Raleigh, NC, USA.

Scientific Reports
|October 4, 2018
PubMed

Insights

Mouse strains vary in their ability to support embryonic stem cell (ESC) derivation. A novel 2iS reprogramming method overcomes genetic barriers, enabling derivation of induced pluripotent stem cells (iPSC) more similar to ESC.

Area of Science:

  • Stem cell biology
  • Genetics
  • Developmental biology

Background:

  • Embryonic stem cells (ESC) derivation is typically restricted to specific Mus musculus strains under leukemia inhibitory factor (LIF) conditions.
  • Other species and some mouse strains form developmentally primed epiblast stem cells (EpiSC) instead of ESC.
  • The permissiveness of different genetic backgrounds to stem cell derivation is not fully understood.

Purpose of the Study:

  • To investigate whether non-permissiveness to ESC derivation extends to induced pluripotent stem cells (iPSC).
  • To identify genetic factors influencing stem cell derivation permissiveness in different mouse strains.
  • To develop a method to overcome non-permissiveness in iPSC derivation.

Main Methods:

  • Derivation of iPSC from eight founder strains of the mouse Collaborative Cross.
  • Genetic analysis to determine the inheritance pattern of non-permissiveness.
  • Development and application of a novel 2iS reprogramming technique using GSK3B and MEK inhibitors with serum.

Main Results:

  • Two mouse strains, NOD/ShiLtJ and WSB/EiJ, were identified as non-permissive for iPSC derivation.
  • Non-permissiveness was found to be a recessive trait, with non-permissive genomes failing to complement.
  • The 2iS reprogramming method successfully overcame genetic background constraints, yielding iPSC transcriptionally similar to ESC.
  • Permissiveness to LIF-dependent stem cell derivation appears to be an evolutionarily derived trait within the Mus musculus lineage.

Conclusions:

  • Genetic background significantly influences the derivation of pluripotent stem cells.
  • The 2iS reprogramming method offers a way to generate ESC-like iPSC across diverse genetic backgrounds.
  • Stem cell derivation permissiveness in Mus musculus is likely a recent evolutionary adaptation.

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