Enforcement of developmental lineage specificity by transcription factor Oct1

• Published in: eLife Vol. 6
• Main Authors: Shen, Zuolian, Kang, Jinsuk, Shakya, Arvind, Tabaka, Marcin, Jarboe, Elke A, Regev, Aviv, Tantin, Dean
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 24.05.2017; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Animals; Cardiomyocytes; Cell Differentiation; Cell self-renewal; Defects; Deoxyribonucleic acid; Developmental Biology and Stem Cells; DNA; Embryo cells; Embryonic stem cells; Gene expression; Gene Expression Regulation, Developmental; Genes and Chromosomes; Genomes; Mice; Microscopy; Morphology; Mouse Embryonic Stem Cells - physiology; Neurogenesis; Observations; Oct-4 protein; Oct1 (Pou2f1); Oct4 (Pou5f1); Octamer Transcription Factor-1 - metabolism; Octamer Transcription Factor-3 - metabolism; Oxidative stress; Physiological aspects; Pluripotency; Stem cell transplantation; Stem cells; Transcription factors; Transcription, Genetic; mouse; stem cells; Oct4 (Pou5f1); genes; developmental biology; embryonic stem cells; chromosomes; Oct1 (Pou2f1)
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.20937

Embryonic stem cells co-express Oct4 and Oct1, a related protein with similar DNA-binding specificity. To study the role of Oct1 in ESC pluripotency and transcriptional control, we constructed germline and inducible-conditional Oct1-deficient ESC lines. ESCs lacking Oct1 show normal appearance, self-renewal and growth but manifest defects upon differentiation. They fail to form beating cardiomyocytes, generate neurons poorly, form small, poorly differentiated teratomas, and cannot generate chimeric mice. Upon RA-mediated differentiation, Oct1-deficient cells induce lineage-appropriate developmentally poised genes poorly while lineage-inappropriate genes, including extra-embryonic genes, are aberrantly expressed. In ESCs, Oct1 co-occupies a specific set of targets with Oct4, but does not occupy differentially expressed developmental targets. Instead, Oct1 occupies these targets as cells differentiate and Oct4 declines. These results identify a dynamic interplay between Oct1 and Oct4, in particular during the critical window immediately after loss of pluripotency when cells make the earliest developmental fate decisions.