TY - JOUR
T1 - Down-regulation of ATF1 leads to early neuroectoderm differentiation of human embryonic stem cells by increasing the expression level of SOX2
AU - Yang, Shang Chih
AU - Liu, Jan Jan
AU - Wang, Cheng Kai
AU - Lin, Yu Tsen
AU - Tsai, Su Yi
AU - Chen, Wei Ju
AU - Huang, Wei Kai
AU - Tu, Po Wen A.
AU - Lin, Yu Chen
AU - Chang, Ching Fang
AU - Cheng, Chih Lun
AU - Lin, Hsuan
AU - Lai, Chien Ying
AU - Lin, Chun Yu
AU - Lee, Yi Hsuan
AU - Chiu, Yen Chun
AU - Hsu, Chiao Ching
AU - Hsu, Shu Ching
AU - Hsiao, Michael
AU - Schuyler, Scott C.
AU - Lu, Frank Leigh
AU - Lu, Jean
N1 - Publisher Copyright:
© FASEB
PY - 2019/9/1
Y1 - 2019/9/1
N2 - We reveal by high-throughput screening that activating transcription factor 1 (ATF1) is a novel pluripotent regulator in human embryonic stem cells (hESCs). The knockdown of ATF1 expression significantly up-regulated neuroectoderm (NE) genes but not mesoderm, endoderm, and trophectoderm genes. Of note, down-regulation or knockout of ATF1 with short hairpin RNA (shRNA), small interfering RNA (siRNA), or clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) was sufficient to up-regulate sex-determining region Y-box (SOX)2 and paired box 6 (PAX6) expression under the undifferentiated or differentiated conditions, whereas overexpression of ATF1 suppressed NE differentiation. Endogenous ATF1 was spontaneously down-regulated after d 1–3 of neural induction. By double-knockdown experiments, up-regulation of SOX2 was critical for the increase of PAX6 and SOX1 expression in shRNA targeting Atf1 hESCs. Using the luciferase reporter assay, we identified ATF1 as a negative transcriptional regulator of Sox2 gene expression. A novel function of ATF1 was discovered, and these findings contribute to a broader understanding of the very first steps in regulating NE differentiation in hESCs.—Yang, S.-C, Liu, J.-J., Wang, C.-K., Lin, Y.-T., Tsai, S.-Y., Chen, W.-J., Huang, W.-K., Tu, P.-W. A., Lin, Y.-C, Chang, C.-F., Cheng, C.-L., Lin, H., Lai, C.-Y., Lin, C.-Y., Lee, Y.-H., Chiu, Y.-C., Hsu, C.-C., Hsu, S.-C., Hsiao, M., Schuyler, S. C., Lu, F. L., Lu, J. Down-regulation of ATF1 leads to early neuroectoderm differentiation of human embryonic stem cells by increasing the expression level of SOX2. FASEB J. 33, 10577–10592 (2019). www.fasebj.org.
AB - We reveal by high-throughput screening that activating transcription factor 1 (ATF1) is a novel pluripotent regulator in human embryonic stem cells (hESCs). The knockdown of ATF1 expression significantly up-regulated neuroectoderm (NE) genes but not mesoderm, endoderm, and trophectoderm genes. Of note, down-regulation or knockout of ATF1 with short hairpin RNA (shRNA), small interfering RNA (siRNA), or clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) was sufficient to up-regulate sex-determining region Y-box (SOX)2 and paired box 6 (PAX6) expression under the undifferentiated or differentiated conditions, whereas overexpression of ATF1 suppressed NE differentiation. Endogenous ATF1 was spontaneously down-regulated after d 1–3 of neural induction. By double-knockdown experiments, up-regulation of SOX2 was critical for the increase of PAX6 and SOX1 expression in shRNA targeting Atf1 hESCs. Using the luciferase reporter assay, we identified ATF1 as a negative transcriptional regulator of Sox2 gene expression. A novel function of ATF1 was discovered, and these findings contribute to a broader understanding of the very first steps in regulating NE differentiation in hESCs.—Yang, S.-C, Liu, J.-J., Wang, C.-K., Lin, Y.-T., Tsai, S.-Y., Chen, W.-J., Huang, W.-K., Tu, P.-W. A., Lin, Y.-C, Chang, C.-F., Cheng, C.-L., Lin, H., Lai, C.-Y., Lin, C.-Y., Lee, Y.-H., Chiu, Y.-C., Hsu, C.-C., Hsu, S.-C., Hsiao, M., Schuyler, S. C., Lu, F. L., Lu, J. Down-regulation of ATF1 leads to early neuroectoderm differentiation of human embryonic stem cells by increasing the expression level of SOX2. FASEB J. 33, 10577–10592 (2019). www.fasebj.org.
KW - early development
KW - gatekeeper
KW - high-throughput screen
UR - https://www.scopus.com/pages/publications/85071782696
U2 - 10.1096/fj.201800220RR
DO - 10.1096/fj.201800220RR
M3 - 文章
C2 - 31242772
AN - SCOPUS:85071782696
SN - 0892-6638
VL - 33
SP - 10577
EP - 10592
JO - FASEB Journal
JF - FASEB Journal
IS - 9
ER -
