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

Phong Nguyen, Georgina Elizabeth Hollway, Carmen Sonntag, Lee Barry Miles, Thomas Edward Hall, Silke Berger, Kristine Joy Fernandez, David Gurevich, Nicholas James Cole, Sara Alaei Shehni, Mirana Soa Manarivo Ramialison, Robert Lyndsey Sutherland, Jose Maria Polo, Graham Lieschke, Peter David Currie

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Haematopoietic 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.
Original languageEnglish
Pages (from-to)314 - 318
Number of pages5
JournalNature
Volume512
Issue number7514
DOIs
Publication statusPublished - 2014

Cite this

Nguyen, Phong ; Hollway, Georgina Elizabeth ; Sonntag, Carmen ; Miles, Lee Barry ; Hall, Thomas Edward ; Berger, Silke ; Fernandez, Kristine Joy ; Gurevich, David ; Cole, Nicholas James ; Alaei Shehni, Sara ; Ramialison, Mirana Soa Manarivo ; Sutherland, Robert Lyndsey ; Polo, Jose Maria ; Lieschke, Graham ; Currie, Peter David. / Haematopoietic stem cell induction by somite-derived endothelial cells controlled by meox1. In: Nature. 2014 ; Vol. 512, No. 7514. pp. 314 - 318.
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title = "Haematopoietic stem cell induction by somite-derived endothelial cells controlled by meox1",
abstract = "Haematopoietic 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.",
author = "Phong Nguyen and Hollway, {Georgina Elizabeth} and Carmen Sonntag and Miles, {Lee Barry} and Hall, {Thomas Edward} and Silke Berger and Fernandez, {Kristine Joy} and David Gurevich and Cole, {Nicholas James} and {Alaei Shehni}, Sara and Ramialison, {Mirana Soa Manarivo} and Sutherland, {Robert Lyndsey} and Polo, {Jose Maria} and Graham Lieschke and Currie, {Peter David}",
year = "2014",
doi = "10.1038/nature13678",
language = "English",
volume = "512",
pages = "314 -- 318",
journal = "Nature",
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number = "7514",

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Haematopoietic stem cell induction by somite-derived endothelial cells controlled by meox1. / Nguyen, Phong; Hollway, Georgina Elizabeth; Sonntag, Carmen; Miles, Lee Barry; Hall, Thomas Edward; Berger, Silke; Fernandez, Kristine Joy; Gurevich, David; Cole, Nicholas James; Alaei Shehni, Sara; Ramialison, Mirana Soa Manarivo; Sutherland, Robert Lyndsey; Polo, Jose Maria; Lieschke, Graham; Currie, Peter David.

In: Nature, Vol. 512, No. 7514, 2014, p. 314 - 318.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Haematopoietic stem cell induction by somite-derived endothelial cells controlled by meox1

AU - Nguyen, Phong

AU - Hollway, Georgina Elizabeth

AU - Sonntag, Carmen

AU - Miles, Lee Barry

AU - Hall, Thomas Edward

AU - Berger, Silke

AU - Fernandez, Kristine Joy

AU - Gurevich, David

AU - Cole, Nicholas James

AU - Alaei Shehni, Sara

AU - Ramialison, Mirana Soa Manarivo

AU - Sutherland, Robert Lyndsey

AU - Polo, Jose Maria

AU - Lieschke, Graham

AU - Currie, Peter David

PY - 2014

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N2 - Haematopoietic 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.

AB - Haematopoietic 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.

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