Signaling from the Sympathetic Nervous System Regulates Hematopoietic Stem Cell Emergence during Embryogenesis

Simon R. Fitch; Gillian M. Kimber; Nicola K. Wilson; Aimee Parker; Bahar Mirshekar-Syahkal; Berthold Goettgens; Alexander Medvinsky; Elaine Dzierzak; Katrin Ottersbach

doi:10.1016/j.stem.2012.07.002

Signaling from the Sympathetic Nervous System Regulates Hematopoietic Stem Cell Emergence during Embryogenesis

Simon R. Fitch, Gillian M. Kimber, Nicola K. Wilson, Aimee Parker, Bahar Mirshekar-Syahkal, Berthold Goettgens, Alexander Medvinsky, Elaine Dzierzak, Katrin Ottersbach

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Abstract / Description of output

The first adult-repopulating hematopoietic stem cells (HSCs) emerge in the aorta-gonads-mesonephros (AGM) region of the embryo. We have recently identified
the transcription factor Gata3 as being upregulated in this tissue specifically at the time of HSC emergence. We now demonstrate that the production of functional and phenotypic HSCs in the AGM is impaired in the absence of Gata3. Furthermore, we show that this effect on HSC generation is secondary to the role of Gata3 in the production of catecholamines, the mediators of the sympathetic
nervous system (SNS), thus making these molecules key components of the AGM HSC niche. These findings demonstrate that the recently described functional
interplay between the hematopoietic system and the SNS extends to the earliest stages of their codevelopment and highlight the fact that HSC development needs to be viewed in the context of the development of other organs.

Original language	English
Pages (from-to)	554-566
Journal	Cell Stem Cell
Volume	11
Issue number	4
DOIs	https://doi.org/10.1016/j.stem.2012.07.002
Publication status	Published - 1 Oct 2012

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title = "Signaling from the Sympathetic Nervous System Regulates Hematopoietic Stem Cell Emergence during Embryogenesis",

abstract = "The first adult-repopulating hematopoietic stem cells (HSCs) emerge in the aorta-gonads-mesonephros (AGM) region of the embryo. We have recently identifiedthe transcription factor Gata3 as being upregulated in this tissue specifically at the time of HSC emergence. We now demonstrate that the production of functional and phenotypic HSCs in the AGM is impaired in the absence of Gata3. Furthermore, we show that this effect on HSC generation is secondary to the role of Gata3 in the production of catecholamines, the mediators of the sympatheticnervous system (SNS), thus making these molecules key components of the AGM HSC niche. These findings demonstrate that the recently described functionalinterplay between the hematopoietic system and the SNS extends to the earliest stages of their codevelopment and highlight the fact that HSC development needs to be viewed in the context of the development of other organs.",

author = "Fitch, {Simon R.} and Kimber, {Gillian M.} and Wilson, {Nicola K.} and Aimee Parker and Bahar Mirshekar-Syahkal and Berthold Goettgens and Alexander Medvinsky and Elaine Dzierzak and Katrin Ottersbach",

year = "2012",

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doi = "10.1016/j.stem.2012.07.002",

language = "English",

volume = "11",

pages = "554--566",

journal = "Cell Stem Cell",

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T1 - Signaling from the Sympathetic Nervous System Regulates Hematopoietic Stem Cell Emergence during Embryogenesis

AU - Fitch, Simon R.

AU - Kimber, Gillian M.

AU - Wilson, Nicola K.

AU - Parker, Aimee

AU - Mirshekar-Syahkal, Bahar

AU - Goettgens, Berthold

AU - Medvinsky, Alexander

AU - Dzierzak, Elaine

AU - Ottersbach, Katrin

PY - 2012/10/1

Y1 - 2012/10/1

N2 - The first adult-repopulating hematopoietic stem cells (HSCs) emerge in the aorta-gonads-mesonephros (AGM) region of the embryo. We have recently identifiedthe transcription factor Gata3 as being upregulated in this tissue specifically at the time of HSC emergence. We now demonstrate that the production of functional and phenotypic HSCs in the AGM is impaired in the absence of Gata3. Furthermore, we show that this effect on HSC generation is secondary to the role of Gata3 in the production of catecholamines, the mediators of the sympatheticnervous system (SNS), thus making these molecules key components of the AGM HSC niche. These findings demonstrate that the recently described functionalinterplay between the hematopoietic system and the SNS extends to the earliest stages of their codevelopment and highlight the fact that HSC development needs to be viewed in the context of the development of other organs.

AB - The first adult-repopulating hematopoietic stem cells (HSCs) emerge in the aorta-gonads-mesonephros (AGM) region of the embryo. We have recently identifiedthe transcription factor Gata3 as being upregulated in this tissue specifically at the time of HSC emergence. We now demonstrate that the production of functional and phenotypic HSCs in the AGM is impaired in the absence of Gata3. Furthermore, we show that this effect on HSC generation is secondary to the role of Gata3 in the production of catecholamines, the mediators of the sympatheticnervous system (SNS), thus making these molecules key components of the AGM HSC niche. These findings demonstrate that the recently described functionalinterplay between the hematopoietic system and the SNS extends to the earliest stages of their codevelopment and highlight the fact that HSC development needs to be viewed in the context of the development of other organs.

U2 - 10.1016/j.stem.2012.07.002

DO - 10.1016/j.stem.2012.07.002

M3 - Article

SN - 1934-5909

VL - 11

SP - 554

EP - 566

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 4

ER -

Signaling from the Sympathetic Nervous System Regulates Hematopoietic Stem Cell Emergence during Embryogenesis

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