PMID- 29321513
OWN - NLM
STAT- MEDLINE
DCOM- 20181116
LR  - 20211204
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 8
IP  - 1
DP  - 2018 Jan 10
TI  - Tousled-like kinase 1 is a negative regulator of core transcription factors in 
      murine embryonic stem cells.
PG  - 334
LID - 10.1038/s41598-017-18628-9 [doi]
LID - 334
AB  - Although the differentiation of pluripotent cells in embryonic stem cells (ESCs) 
      is often associated with protein kinase-mediated signaling pathways and 
      Tousled-like kinase 1 (Tlk1) is required for development in several species, the 
      role of Tlk1 in ESC function remains unclear. Here, we used mouse ESCs to study 
      the function of Tlk1 in pluripotent cells. The knockdown (KD)-based 
      Tlk1-deficient cells showed that Tlk1 is not essential for ESC self-renewal in an 
      undifferentiated state. However, Tlk1-KD cells formed irregularly shaped embryoid 
      bodies and induced resistance to differentiation cues, indicating their failure 
      to differentiate into an embryoid body. Consistent with their failure to 
      differentiate, Tlk1-KD cells failed to downregulate the expression of 
      undifferentiated cell markers including Oct4, Nanog, and Sox2 during 
      differentiation, suggesting a negative role of Tlk1. Interestingly, Tlk1 
      overexpression sufficiently downregulated the expression of core pluripotency 
      factors possibly irrespective of its kinase activity, thereby leading to a 
      partial loss of self-renewal ability even in an undifferentiated state. Moreover, 
      Tlk1 overexpression caused severe growth defects and G(2)/M phase arrest as well 
      as apoptosis. Collectively, our data suggest that Tlk1 negatively regulates the 
      expression of pluripotency factors, thereby contributing to the scheduled 
      differentiation of mouse ESCs.
FAU - Lee, Jina
AU  - Lee J
AD  - Department of Systems Biology, College of Life Science and Biotechnology, Yonsei 
      University, Seoul, 03722, Republic of Korea.
AD  - Initiative for Biological Function and Systems, Yonsei University, Seoul, 03722, 
      Republic of Korea.
FAU - Kim, Min Seong
AU  - Kim MS
AD  - Department of Systems Biology, College of Life Science and Biotechnology, Yonsei 
      University, Seoul, 03722, Republic of Korea.
AD  - Initiative for Biological Function and Systems, Yonsei University, Seoul, 03722, 
      Republic of Korea.
FAU - Park, Su Hyung
AU  - Park SH
AD  - Department of Systems Biology, College of Life Science and Biotechnology, Yonsei 
      University, Seoul, 03722, Republic of Korea.
AD  - Initiative for Biological Function and Systems, Yonsei University, Seoul, 03722, 
      Republic of Korea.
AD  - Center for Genomic Integrity, Institute for Basic Science, Ulsan National 
      Institute of Science and Technology, UNIST-gil 50, Ulsan, 689-798, Republic of 
      Korea.
FAU - Jang, Yeun Kyu
AU  - Jang YK
AUID- ORCID: 0000-0002-1342-4190
AD  - Department of Systems Biology, College of Life Science and Biotechnology, Yonsei 
      University, Seoul, 03722, Republic of Korea. ykjang@yonsei.ac.kr.
AD  - Initiative for Biological Function and Systems, Yonsei University, Seoul, 03722, 
      Republic of Korea. ykjang@yonsei.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180110
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Leukemia Inhibitory Factor)
RN  - 0 (Lif protein, mouse)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.1.- (Tlk1 protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/genetics
MH  - Cell Cycle/genetics
MH  - Cell Differentiation/drug effects/genetics
MH  - Cells, Cultured
MH  - Ectopic Gene Expression
MH  - Embryonic Stem Cells/cytology/drug effects/*metabolism
MH  - Gene Expression Regulation
MH  - Gene Knockout Techniques
MH  - Leukemia Inhibitory Factor/metabolism/pharmacology
MH  - Mice
MH  - Protein Binding
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
MH  - Transcription Factors/*metabolism
MH  - Transcription, Genetic
PMC - PMC5762884
COIS- The authors declare that they have no competing interests.
EDAT- 2018/01/13 06:00
MHDA- 2018/11/18 06:00
PMCR- 2018/01/10
CRDT- 2018/01/12 06:00
PHST- 2017/09/07 00:00 [received]
PHST- 2017/12/13 00:00 [accepted]
PHST- 2018/01/12 06:00 [entrez]
PHST- 2018/01/13 06:00 [pubmed]
PHST- 2018/11/18 06:00 [medline]
PHST- 2018/01/10 00:00 [pmc-release]
AID - 10.1038/s41598-017-18628-9 [pii]
AID - 18628 [pii]
AID - 10.1038/s41598-017-18628-9 [doi]
PST - epublish
SO  - Sci Rep. 2018 Jan 10;8(1):334. doi: 10.1038/s41598-017-18628-9.