Jak2 and Tyk2 are necessary for lineage-specific differentiation, but not for the maintenance of self-renewal of mouse embryonic stem cells.
As the LIF-induced Jak1/STAT3 pathway has been reported to play a crucial role in self-renewal of mESCs, we sought to determine if Jak2, which is also expressed in mESCs, might also be involved in the pathway. By employing an RNAi strategy, we established both Jak2 and Jak2/Tyk2 knockdown mESC clones. Both Jak2 and Jak2/Tyk2 knockdown clones maintained the undifferentiated state as wild-type controls, even in a very low concentration of LIF. However, we observed not only faster onset of differentiation but also differential expression of tissue-specific lineage genes for ectodermal and mesodermal, but not endodermal origins from embryoid bodies generated from both types of knockdown clones compared to the wild-type. Furthermore, the reduced level of Jak2 caused differentiation of mESCs in the presence of LIF when the Wnt pathway was activated by LiCl treatment. Taken together, we demonstrated that Jak2 and Tyk2 are not involved in LIF-induced STAT3 pathway for self-renewal of mESCs, but play a role in early lineage decision of mESCs to various differentiated cell types.
Chung
Bo Mee
BM
Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.
Kang
Ho Chul
HC
Han
Su Youne
SY
Heo
Hyen Seok
HS
Lee
Jong Joo
JJ
Jeon
Jinseon
J
Lim
Ji Young
JY
Shin
Incheol
I
Hong
Seung Hwan
SH
Cho
Yoon Shin
YS
Kim
Chul Geun
CG
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000378:metabolism*; D051379:Mice; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D053634:TYK2 Kinase / Q000378:metabolism*
D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; D053634:TYK2 Kinase; C499356:Tyk2 protein, mouse