Jak1/Stat3 signaling acts as a positive regulator of pluripotency in chicken pre-gastrula embryos.
Pluripotent cells emerging at very early stages of development are the founders of differentiated cells. It has been established in mouse that the LIF/Jak/Stat-Nanog axis acts as a positive regulator to support the pluripotent state of cells whereas Fgf/Erk signaling acts as a negative regulator to direct cells to enter the differentiating state. In chicken, although Fgf/Erk signaling is known to act as a negative regulator, positive regulators remained unknown. Here, to identify positive regulator(s) of chicken pluripotency, we selected Jak1/Stat3 signaling as a candidate based on transcriptome analyses. Jak1/Stat3 signaling was activated specifically at stages before gastrulation: Stat3 protein was localized in nuclei at blastodermal stages, but translocated to cytoplasm after gastrulation. We conducted pharmacological and gene transfection analyses in the blastoderm-derived colony formation assay, in which Nanog-positive dense colonies represent a hallmark of the undifferentiated state, and found that Jak1/Stat3 signaling supports pluripotency in chicken early embryos. Jak1 inhibition abolished the formation of dense colonies, but the colony formation was restored when Stat3ER was artificially activated. We propose that the molecular mechanisms regulating pluripotency are conserved at the signaling network level between mouse and chicken, and possibly among a wider range of species.
Department of Biophysics, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan. Electronic address: nakanoh@nibb.ac.jp.
Shota
S
Nakanoh
Department of Biophysics, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan; Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Naoyuki
N
Fuse
Department of Zoology, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
Ryosuke
R
Tadokoro
Department of Zoology, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan; AMED Core Research for Evolutional Science and Technology (AMED-CREST), Japan Agency for Medical Research and Development (AMED), Chiyoda-ku, Tokyo 100-0004, Japan.
Yoshiko
Y
Takahashi
Department of Biophysics, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan. Electronic address: kiyokazu.agata@gakushuin.ac.jp.
Kiyokazu
K
Agata
D000818:Animals; D001756:Blastoderm / Q000166:cytology; D002467:Cell Nucleus / Q000378:metabolism; D002642:Chick Embryo; D002645:Chickens; D005775:Gastrula / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D015850:Interleukin-6 / Q000378:metabolism; D053613:Janus Kinase 1 / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D021381:Protein Transport; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000235:genetics
D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D000071223:Suppressor of Cytokine Signaling 3 Protein; D053613:Janus Kinase 1
Blastoderm; IL6/Jak1/Stat3; Nanog; Pluripotent state