title: Hesx1 enhances pluripotency by working downstream of multiple pluripotency-associated signaling pathways.
abstract: Hesx1, a homeobox gene expressed in embryonic stem cells (ESCs), has been implicated in the core transcription factors governing the pluripotent state. However, data about the underlying mechanism of how Hesx1 is involved in maintaining pluripotency is still scarce. In this study, we find Hesx1 responds to multiple pluripotency-related pathway inhibitors as well as LIF stimulation. Particularly, the expression of Hesx1 can be readily induced by dual inhibition (2i) of glycogen synthase kinase 3 and mitogen-activated protein kinase. Forced expression of Hesx1 can partially compensate for the withdrawal of either LIF or each component of 2i. We also demonstrate that LIF and each inhibitor of 2i can induce Hesx1 independent of one another. We tentatively put forward that Hesx1 is a common downstream target of LIF- and 2i-mediated self-renewal signaling pathways and plays an important role in maintaining ESC identity. Our study extends the methods of identifying the missing crucial factors in establishing ESC pluripotency.
authors.affiliation: College of Life Sciences, Northwest A&F University, Yangling 712100, PR China; Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling 712100, PR China.
authors.forename: Wen-Zhong
authors.initials: WZ
authors.lastname: Li
authors.affiliation: School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, PR China.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Northwest A&F University, Yangling 712100, PR China; Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling 712100, PR China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Chen
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, PR China; Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling 712100, PR China.
authors.forename: Hong-Ni
authors.initials: HN
authors.lastname: Xue
authors.affiliation: School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 200240 Shanghai, PR China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, PR China; Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling 712100, PR China. Electronic address: gzknwaf@126.com.
authors.forename: Ze-Kun
authors.initials: ZK
authors.lastname: Guo
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, PR China; Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling 712100, PR China. Electronic address: zylabnwaf@126.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D008822:Mice, Transgenic; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000235:genetics; D015398:Signal Transduction; D014212:Tretinoin / Q000494:pharmacology
chemical_list: C489733:Hesx1 protein, mouse; D018398:Homeodomain Proteins; D053605:Leukemia Inhibitory Factor; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014212:Tretinoin; D038362:Glycogen Synthase Kinase 3
keywords: Common downstream target; Hesx1; Pluripotency; Signaling pathways