FOXF1 inhibits hematopoietic lineage commitment during early mesoderm specification.
AffiliationCancer Research UK Stem Cell Hematopoiesis Group, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, M20 4BX, UK
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AbstractThe 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 increase commitment toward primitive erythropoiesis in Foxf1 deficient embryos while 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.
CitationFOXF1 inhibits hematopoietic lineage commitment during early mesoderm specification. 2015: Development
- The forkhead transcription factor Foxf1 is required for differentiation of extra-embryonic and lateral plate mesoderm.
- Authors: Mahlapuu M, Ormestad M, Enerbäck S, Carlsson P
- Issue date: 2001 Jan
- Multiple mesoderm subsets give rise to endothelial cells, whereas hematopoietic cells are differentiated only from a restricted subset in embryonic stem cell differentiation culture.
- Authors: Era T, Izumi N, Hayashi M, Tada S, Nishikawa S, Nishikawa S
- Issue date: 2008 Feb
- Mesoderm is committed to hemato-endothelial and cardiac lineages in human embryoid bodies by sequential exposure to cytokines.
- Authors: Zhu MX, Zhao JY, Chen GA
- Issue date: 2013 Jan 1
- Endocardial cells are a distinct endothelial lineage derived from Flk1+ multipotent cardiovascular progenitors.
- Authors: Misfeldt AM, Boyle SC, Tompkins KL, Bautch VL, Labosky PA, Baldwin HS
- Issue date: 2009 Sep 1
- Expressions of PDGF receptor alpha, c-Kit and Flk1 genes clustering in mouse chromosome 5 define distinct subsets of nascent mesodermal cells.
- Authors: Kataoka H, Takakura N, Nishikawa S, Tsuchida K, Kodama H, Kunisada T, Risau W, Kita T, Nishikawa SI
- Issue date: 1997 Dec