Haematopoietic stem cell induction by somite-derived endothelial cells controlled by meox1

Simple item page
dc.contributor.authorNguyen, P.D.
dc.contributor.authorHollway, G.E.
dc.contributor.authorSonntag, C.
dc.contributor.authorMiles, L.B.
dc.contributor.authorHall, T.E.
dc.contributor.authorBerger, S.
dc.contributor.authorFernandez, K.J.
dc.contributor.authorGurevich, D.B.
dc.contributor.authorCole, N.J.
dc.contributor.authorAlaei, S.
dc.contributor.authorRamialison, M.
dc.contributor.authorSutherland, R.L.
dc.contributor.authorPolo, J.M.
dc.contributor.authorLieschke, G.J.
dc.contributor.authorCurrie, P.D.
dc.date.issued2014
dc.description.abstractHaematopoietic stem cells (HSCs) are self-renewing stem cells capable of replenishing all blood lineages. In all vertebrate embryos that have been studied, definitive HSCs are generated initially within the dorsal aorta (DA) of the embryonic vasculature by a series of poorly understood inductive events. Previous studies have identified that signalling relayed from adjacent somites coordinates HSC induction, but the nature of this signal has remained elusive. Here we reveal that somite specification of HSCs occurs via the deployment of a specific endothelial precursor population, which arises within a sub-compartment of the zebrafish somite that we have defined as the endotome. Endothelial cells of the endotome are specified within the nascent somite by the activity of the homeobox gene meox1. Specified endotomal cells consequently migrate and colonize the DA, where they induce HSC formation through the deployment of chemokine signalling activated in these cells during endotome formation. Loss of meox1 activity expands the endotome at the expense of a second somitic cell type, the muscle precursors of the dermomyotomal equivalent in zebrafish, the external cell layer. The resulting increase in endotome-derived cells that migrate to colonize the DA generates a dramatic increase in chemokine-dependent HSC induction. This study reveals the molecular basis for a novel somite lineage restriction mechanism and defines a new paradigm in induction of definitive HSCs.
dc.description.statementofresponsibilityPhong Dang Nguyen, Georgina Elizabeth Hollway, Carmen Sonntag, Lee Barry Miles, Thomas Edward Hall, Silke Berger ... et al.
dc.identifier.citationNature, 2014; 512(7514):314-318
dc.identifier.doi10.1038/nature13678
dc.identifier.issn0028-0836
dc.identifier.issn1476-4687
dc.identifier.orcidPolo, J.M. [0000-0002-2531-778X]
dc.identifier.urihttps://hdl.handle.net/2440/133536
dc.language.isoen
dc.publisherNature Publishing Group
dc.relation.grantARC
dc.relation.grantNHMRC
dc.rights© 2014 Macmillan Publishers Limited. All rights reserved.
dc.source.urihttps://doi.org/10.1038/nature13678
dc.subjectMuscles
dc.subjectAorta
dc.subjectHematopoietic Stem Cells
dc.subjectEndothelial Cells
dc.subjectChick Embryo
dc.subjectSomites
dc.subjectAnimals
dc.subjectZebrafish
dc.subjectHumans
dc.subjectMice
dc.subjectHomeodomain Proteins
dc.subjectZebrafish Proteins
dc.subjectTranscription Factors
dc.subjectCell Movement
dc.subjectMutation
dc.subjectWnt Proteins
dc.subjectChemokine CXCL12
dc.subjectBiomarkers
dc.subject.meshMuscles
dc.subject.meshAorta
dc.subject.meshHematopoietic Stem Cells
dc.subject.meshEndothelial Cells
dc.subject.meshChick Embryo
dc.subject.meshSomites
dc.subject.meshAnimals
dc.subject.meshZebrafish
dc.subject.meshHumans
dc.subject.meshMice
dc.subject.meshHomeodomain Proteins
dc.subject.meshZebrafish Proteins
dc.subject.meshTranscription Factors
dc.subject.meshCell Movement
dc.subject.meshMutation
dc.subject.meshWnt Proteins
dc.subject.meshChemokine CXCL12
dc.subject.meshBiomarkers
dc.titleHaematopoietic stem cell induction by somite-derived endothelial cells controlled by meox1
dc.typeJournal article
pubs.publication-statusPublished

Files

Collections

Medicine publications