title: Interplay between SOX7 and RUNX1 regulates hemogenic endothelial fate in the yolk sac.
abstract: Endothelial to hematopoietic transition (EHT) is a dynamic process involving the shutting down of endothelial gene expression and switching on of hematopoietic gene transcription. Although the factors regulating EHT in hemogenic endothelium (HE) of the dorsal aorta have been relatively well studied, the molecular regulation of yolk sac HE remains poorly understood. Here, we show that SOX7 inhibits the expression of RUNX1 target genes in HE, while having no effect on RUNX1 expression itself. We establish that SOX7 directly interacts with RUNX1 and inhibits its transcriptional activity. Through this interaction we demonstrate that SOX7 hinders RUNX1 DNA binding as well as the interaction between RUNX1 and its co-factor CBFβ. Finally, we show by single-cell expression profiling and immunofluorescence that SOX7 is broadly expressed across the RUNX1+yolk sac HE population compared with SOX17. Collectively, these data demonstrate for the first time how direct protein-protein interactions between endothelial and hematopoietic transcription factors regulate contrasting transcriptional programs during HE differentiation and EHT.
authors: Stem Cell Hematopoiesis, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK.
authors: Andrew J
authors: AJ
authors: Lilly
authors: Stem Cell Hematopoiesis, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK.
authors: Guilherme
authors: G
authors: Costa
authors: Stem Cell Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK.
authors: Anne
authors: A
authors: Largeot
authors: Stem Cell Hematopoiesis, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK.
authors: Muhammad Z H
authors: MZ
authors: Fadlullah
authors: Stem Cell Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK.
authors: Michael
authors: M
authors: Lie-A-Ling
authors: Stem Cell Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK valerie.kouskoff@manchester.ac.uk georges.lacaud@cruk.manchester.ac.uk.
authors: Georges
authors: G
authors: Lacaud
authors: Stem Cell Hematopoiesis, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK valerie.kouskoff@manchester.ac.uk georges.lacaud@cruk.manchester.ac.uk.
authors: Valerie
authors: 0000-0001-9801-4993
authors: V
authors: Kouskoff
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors; D004727:Endothelium / Q000166:cytology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005260:Female; D024002:HMGB Proteins / Q000378:metabolism; D055018:Hemangioblasts / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055760:SOXF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D015017:Yolk Sac / Q000166:cytology*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D024002:HMGB Proteins; C493726:Runx1 protein, mouse; D055760:SOXF Transcription Factors; C511606:Sox17 protein, mouse; C102515:Sox7 protein, mouse
keywords: EHT; Hemogenic endothelium; RUNX1; SOX7; Yolk sac