Inductive interactions mediated by interplay of asymmetric signalling underlie development of adult hematopoietic stem cells

Céline Souilhol; Christèle Gonneau; Javier G. Lendinez; Antoniana Batsivari; Stanislav Rybtsov; Heather Wilson; Lucia Morgado-Palacin; David Hills; Samir Taoudi; Jennifer Antonchuk; Suling Zhao; Alexander Medvinsky

doi:10.1038/ncomms10784

Inductive interactions mediated by interplay of asymmetric signalling underlie development of adult hematopoietic stem cells

Céline Souilhol, Christèle Gonneau, Javier G. Lendinez, Antoniana Batsivari, Stanislav Rybtsov, Heather Wilson, Lucia Morgado-Palacin, David Hills, Samir Taoudi, Jennifer Antonchuk, Suling Zhao, Alexander Medvinsky^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

During embryonic development, adult haematopoietic stem cells (HSCs) emerge preferentially in the ventral domain of the aorta in the aorta–gonad–mesonephros (AGM)region. Several signalling pathways such as Notch, Wnt, Shh and RA are implicated in this process, yet how these interact to regulate the emergence of HSCs has not previously been described in mammals. Using a combination of ex vivo and in vivo approaches, we report here that stage-specific reciprocal dorso–ventral inductive interactions and lateral input from the urogenital ridges are required to drive HSC development in the aorta. Our study strongly suggests that these inductive interactions in the AGM region are mediated by the interplay between spatially polarized signalling pathways. Specifically, Shh produced in the dorsal region of the AGM, stem cell factor in the ventral and lateral regions, and BMP inhibitory signals in the ventral tissue are integral parts of the regulatory system involved in the development of HSCs.

Original language	English
Article number	10784
Number of pages	13
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms10784
Publication status	Published - 8 Mar 2016

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10.1038/ncomms10784Licence: Creative Commons: Attribution (CC-BY)

MedvinskEtalNC2016InductiveinteractionsMediatedByInterplayOfAsymmetricSignallingFinal published version, 1.45 MBLicence: Creative Commons: Attribution (CC-BY)

ECAT (100468) Analysis of the early development of human haematopoietic stem and progenitor cells
Medvinsky, A.
UK-based charities
6/05/13 → 8/10/17
Project: Research

Alexander Medvinsky
- School of Biological Sciences - Professor of Haematopoietic Stem Cell Biology
- Centre for Regenerative Medicine
- Edinburgh Haematopoiesis Network
Person: Academic: Research Active

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Souilhol, C., Gonneau, C., Lendinez, J. G., Batsivari, A., Rybtsov, S., Wilson, H., Morgado-Palacin, L., Hills, D., Taoudi, S., Antonchuk, J., Zhao, S., & Medvinsky, A. (2016). Inductive interactions mediated by interplay of asymmetric signalling underlie development of adult hematopoietic stem cells. Nature Communications, 7, Article 10784. https://doi.org/10.1038/ncomms10784

@article{e182f3daac824aefabbbd48b09d746ee,

title = "Inductive interactions mediated by interplay of asymmetric signalling underlie development of adult hematopoietic stem cells",

abstract = "During embryonic development, adult haematopoietic stem cells (HSCs) emerge preferentially in the ventral domain of the aorta in the aorta–gonad–mesonephros (AGM)region. Several signalling pathways such as Notch, Wnt, Shh and RA are implicated in this process, yet how these interact to regulate the emergence of HSCs has not previously been described in mammals. Using a combination of ex vivo and in vivo approaches, we report here that stage-specific reciprocal dorso–ventral inductive interactions and lateral input from the urogenital ridges are required to drive HSC development in the aorta. Our study strongly suggests that these inductive interactions in the AGM region are mediated by the interplay between spatially polarized signalling pathways. Specifically, Shh produced in the dorsal region of the AGM, stem cell factor in the ventral and lateral regions, and BMP inhibitory signals in the ventral tissue are integral parts of the regulatory system involved in the development of HSCs.",

author = "C{\'e}line Souilhol and Christ{\`e}le Gonneau and Lendinez, {Javier G.} and Antoniana Batsivari and Stanislav Rybtsov and Heather Wilson and Lucia Morgado-Palacin and David Hills and Samir Taoudi and Jennifer Antonchuk and Suling Zhao and Alexander Medvinsky",

note = "This work was supported by LLR, BBSRC, MRC, Wellcome Trust",

year = "2016",

month = mar,

day = "8",

doi = "10.1038/ncomms10784",

language = "English",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

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TY - JOUR

T1 - Inductive interactions mediated by interplay of asymmetric signalling underlie development of adult hematopoietic stem cells

AU - Souilhol, Céline

AU - Gonneau, Christèle

AU - Lendinez, Javier G.

AU - Batsivari, Antoniana

AU - Rybtsov, Stanislav

AU - Wilson, Heather

AU - Morgado-Palacin, Lucia

AU - Hills, David

AU - Taoudi, Samir

AU - Antonchuk, Jennifer

AU - Zhao, Suling

AU - Medvinsky, Alexander

N1 - This work was supported by LLR, BBSRC, MRC, Wellcome Trust

PY - 2016/3/8

Y1 - 2016/3/8

N2 - During embryonic development, adult haematopoietic stem cells (HSCs) emerge preferentially in the ventral domain of the aorta in the aorta–gonad–mesonephros (AGM)region. Several signalling pathways such as Notch, Wnt, Shh and RA are implicated in this process, yet how these interact to regulate the emergence of HSCs has not previously been described in mammals. Using a combination of ex vivo and in vivo approaches, we report here that stage-specific reciprocal dorso–ventral inductive interactions and lateral input from the urogenital ridges are required to drive HSC development in the aorta. Our study strongly suggests that these inductive interactions in the AGM region are mediated by the interplay between spatially polarized signalling pathways. Specifically, Shh produced in the dorsal region of the AGM, stem cell factor in the ventral and lateral regions, and BMP inhibitory signals in the ventral tissue are integral parts of the regulatory system involved in the development of HSCs.

AB - During embryonic development, adult haematopoietic stem cells (HSCs) emerge preferentially in the ventral domain of the aorta in the aorta–gonad–mesonephros (AGM)region. Several signalling pathways such as Notch, Wnt, Shh and RA are implicated in this process, yet how these interact to regulate the emergence of HSCs has not previously been described in mammals. Using a combination of ex vivo and in vivo approaches, we report here that stage-specific reciprocal dorso–ventral inductive interactions and lateral input from the urogenital ridges are required to drive HSC development in the aorta. Our study strongly suggests that these inductive interactions in the AGM region are mediated by the interplay between spatially polarized signalling pathways. Specifically, Shh produced in the dorsal region of the AGM, stem cell factor in the ventral and lateral regions, and BMP inhibitory signals in the ventral tissue are integral parts of the regulatory system involved in the development of HSCs.

U2 - 10.1038/ncomms10784

DO - 10.1038/ncomms10784

M3 - Article

AN - SCOPUS:84960386356

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 10784

ER -

Inductive interactions mediated by interplay of asymmetric signalling underlie development of adult hematopoietic stem cells

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ECAT (100468) Analysis of the early development of human haematopoietic stem and progenitor cells

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Alexander Medvinsky

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