Journal
DEVELOPMENT
Volume 142, Issue 3, Pages 431-437Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.112375
Keywords
LIF signaling; MAP kinase; Stat3; Embryonic stem cell; Signal responsiveness
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Funding
- Research Program of Innovative Cell Biology by Innovative Technology (Cell Innovation) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan
- Japan Science and Technology Agency (JST) CREST program
- RIKEN grant
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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.
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