Extrinsic factors derived from mouse embryonal carcinoma cell lines maintain pluripotency of mouse embryonic stem cells through a novel signal pathway.
Embryonic carcinoma (EC) cells, which are malignant stem cells of teratocarcinoma, have numerous morphological and biochemical properties in common with pluripotent stem cells such as embryonic stem (ES) cells. However, three EC cell lines (F9, P19 and PCC3) show different developmental potential and self-renewal capacity from those of ES cells. All three EC cell lines maintain self-renewal capacity in serum containing medium without Leukemia Inhibitory factor (LIF) or feeder layer, and show limited differentiation capacity into restricted lineage and cell types. To reveal the underlying mechanism of these characteristics, we took the approach of characterizing extrinsic factors derived from EC cells on the self-renewal capacity and pluripotency of mouse ES cells. Here we demonstrate that EC cell lines F9 and P19 produce factor(s) maintaining the undifferentiated state of mouse ES cells via an unidentified signal pathway, while P19 and PCC3 cells produce self-renewal factors of ES cells other than LIF that were able to activate the STAT3 signal; however, inhibition of STAT3 activation with Janus kinase inhibitor shows only partial impairment on the maintenance of the undifferentiated state of ES cells. Thus, these factors present in EC cells-derived conditioned medium may be responsible for the self-renewal capacity of EC and ES cells independently of LIF signaling.
Kawazoe
Shinjirou
S
Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medical Sciences, Tottori University, Nishi-cho, Yonago, Tottori, Japan.
Ikeda
Nobuhito
N
Miki
Kengo
K
Shibuya
Masayuki
M
Morikawa
Kumi
K
Nakano
Seiji
S
Oshimura
Mitsuo
M
Hisatome
Ichiro
I
Shirayoshi
Yasuaki
Y
D000818:Animals; D001685:Biological Factors / Q000378:metabolism / Q000494:pharmacology*; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor / Q000378:metabolism; D003470:Culture Media / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D054278:Embryonal Carcinoma Stem Cells / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D017930:Genes, Reporter; D005855:Germ Layers / Q000166:cytology; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D053605:Leukemia Inhibitory Factor / Q000502:physiology; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction
D001685:Biological Factors; D015415:Biomarkers; D003470:Culture Media; D017077:Culture Media, Conditioned; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D053612:Janus Kinases