title: FOXF1 inhibits hematopoietic lineage commitment during early mesoderm specification.
abstract: The molecular mechanisms orchestrating early mesoderm specification are still poorly understood. In particular, how alternate cell fate decisions are regulated in nascent mesoderm remains mostly unknown. In the present study, we investigated both in vitro in differentiating embryonic stem cells, and in vivo in gastrulating embryos, the lineage specification of early mesodermal precursors expressing or not the Forkhead transcription factor FOXF1. Our data revealed that FOXF1-expressing mesoderm is derived from FLK1(+) progenitors and that in vitro this transcription factor is expressed in smooth muscle and transiently in endothelial lineages, but not in hematopoietic cells. In gastrulating embryos, FOXF1 marks most extra-embryonic mesoderm derivatives including the chorion, the allantois, the amnion and a subset of endothelial cells. Similarly to the in vitro situation, FOXF1 expression is excluded from the blood islands and blood cells. Further analysis revealed an inverse correlation between hematopoietic potential and FOXF1 expression in vivo with increased commitment toward primitive erythropoiesis in Foxf1-deficient embryos, whereas FOXF1-enforced expression in vitro was shown to repress hematopoiesis. Altogether, our data establish that during gastrulation, FOXF1 marks all posterior primitive streak extra-embryonic mesoderm derivatives with the remarkable exception of the blood lineage. Our study further suggests that this transcription factor is implicated in actively restraining the specification of mesodermal progenitors to hematopoiesis.
authors: Cancer Research UK Stem Cell Hematopoiesis Group, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester M20 4BX, UK.
authors: Maud
authors: M
authors: Fleury
authors: Cancer Research UK Stem Cell Hematopoiesis Group, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester M20 4BX, UK.
authors: Alexia
authors: A
authors: Eliades
authors: Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg 40530, Sweden.
authors: Peter
authors: P
authors: Carlsson
authors: Cancer Research UK Stem Cell Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester M20 4BX, UK georges.lacaud@cruk.manchester.ac.uk valerie.kouskoff@cruk.manchester.ac.uk.
authors: Georges
authors: G
authors: Lacaud
authors: Cancer Research UK Stem Cell Hematopoiesis Group, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester M20 4BX, UK georges.lacaud@cruk.manchester.ac.uk valerie.kouskoff@cruk.manchester.ac.uk.
authors: Valerie
authors: V
authors: Kouskoff
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D019070:Cell Lineage / Q000502:physiology*; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D020869:Gene Expression Profiling; D018014:Gene Transfer Techniques; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007150:Immunohistochemistry; D008648:Mesoderm / Q000196:embryology*; D046228:Microarray Analysis; D010957:Plasmids / Q000235:genetics
chemical_list: C098521:FOXF1 protein, human; D051858:Forkhead Transcription Factors
keywords: Gastrulation; Hemangioblast; Mesoderm