The differential activation of intracellular signaling pathways confers the permissiveness of embryonic stem cell derivation from different mouse strains.

Satoshi Ohtsuka,Hitoshi Niwa

doi:10.1242/dev.112375

Satoshi Ohtsuka, Hitoshi Niwa

Open Access

https://doi.org/10.1242/dev.112375

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Journal: Development (Cambridge, England)	Publication Date: Jan 1, 2015
Citations: 19	License type: CC BY 3.0

Affiliation: Kobe University

Abstract

The requirement of leukemia inhibitory factor (LIF) for the establishment and maintenance of mouse embryonic stem cells (ESCs) depends on the genetic background of the ESC origin. To reveal the molecular basis of the strain-dependent function of LIF, we compared the activation of the intracellular signaling pathways downstream of LIF in ESCs with different genetic backgrounds. We found that the JAK-Stat3 pathway was dominantly activated in ESCs derived from ‘permissive’ mouse strains (129Sv and C57BL6), whereas the MAP kinase pathway was hyperactivated in ESCs from ‘non-permissive’ strains (NOD, CBA and FVB). Artificial activation of Stat3 supported stable self-renewal of ESCs from non-permissive strains. These data suggest that the difference in the balance between the two intracellular signaling pathways underlies the differential response to LIF.

Highlights

Mouse embryonic stem cells (ESCs) were first established in fetal calf serum (FCS)-containing medium with mouse embryonic fibroblasts (MEF) feeder cells (Evans and Kaufman, 1981; Martin, 1981)
Comparison of the self-renewing abilities of ESCs derived from different strains Previous reports indicated that there are two types of mouse strains: strains permissive for the establishment of ESCs in FCS/leukemia inhibitory factor (LIF) or FCS/LIF/MEF (129Sv, C57BL6 and BALB/c), and non-permissive strains (NOD, CBA and FVB) (Kawase et al, 1994; Brook et al, 2003; Nagafuchi et al, 1999; Cinelli et al, 2008)
In FCS/LIF, ESCs derived from 129Sv and C57BL6 formed stem-cell colonies at a much higher rate than ESCs derived from the other strains (Fig. 1G)

Summary

Introduction

Mouse embryonic stem cells (ESCs) were first established in fetal calf serum (FCS)-containing medium with mouse embryonic fibroblasts (MEF) feeder cells (Evans and Kaufman, 1981; Martin, 1981). These ESCs continued self-renewal, with maintaining expression of pluripotency-associated genes at comparable levels (Fig. 1A) and compact colony morphologies (Fig. 1C) in 2iLIF.

Results

Conclusion