Embryonic germ cells from mice and rats exhibit properties consistent with a generic pluripotent ground state

Harry G Leitch1, Kate Blair, William Mansfield

  • 1Wellcome Trust Cancer Research UK Gurdon Institute, The Henry Wellcome Building of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.

Development (Cambridge, England)
|June 4, 2010
PubMed

Insights

Dual inhibition (2i) supports self-renewal of mouse and rat embryonic germ (EG) cells, enabling their derivation and contribution to chimeras. This suggests a conserved molecular ground state in pluripotent rodent cells.

Area of Science:

  • Stem cell biology
  • Developmental biology
  • Epigenetics

Background:

  • Mouse and rat embryonic stem cells (ESCs) self-renew in defined medium using dual inhibition (2i) of Erk1/2 and GSK3.
  • Embryonic germ (EG) cells, derived from primordial germ cells, also possess pluripotency but their derivation and self-renewal mechanisms are less understood.
  • Investigating 2i's role in EG cell culture is crucial for understanding pluripotent cell states.

Purpose of the Study:

  • To determine if dual inhibition (2i) supports the derivation and self-renewal of embryonic germ (EG) cells.
  • To assess the potential of 2i-cultured EG cells for contributing to chimeras and germline transmission.
  • To establish EG cell derivation from rats under 2i conditions.

Main Methods:

  • Culturing mouse and rat primordial germ cells in defined medium with 2i and leukemia inhibitory factor (LIF).
  • Assessing EG cell derivation efficiency, self-renewal capacity, and pluripotency markers.
  • Evaluating the contribution of derived EG cells to chimeras, including germline contribution.

Main Results:

  • High-efficiency derivation of mouse EG cells using 2i-LIF, without needing FGF or SCF.
  • Successful derivation of rat EG cells using 2i-LIF for the first time.
  • Derived mouse and rat EG cells contributed extensively to chimeras, including germline transmission, and exhibited diploid karyotypes and genetic manipulability.

Conclusions:

  • Dual inhibition (2i) effectively supports the derivation and self-renewal of both mouse and rat embryonic germ (EG) cells.
  • EG cells derived under 2i conditions are pluripotent and capable of extensive chimera contribution and germline transmission.
  • These findings support a conserved molecular ground state in pluripotent rodent cells, with primordial germ cells potentially being a valuable source for naïve pluripotent stem cells.

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