Cooperative transcription activation by Nurr1 and Pitx3 induces embryonic stem cell maturation to the midbrain dopamine neuron phenotype

Cecile Martinat; Jean-Jacques Bacci; Thomas Leete; Jongpil Kim; William B Vanti; Amy H Newman; Joo H Cha; Ulrik Gether; Honggang Wang; Asa Abeliovich

doi:10.1073/pnas.0511153103

Cooperative transcription activation by Nurr1 and Pitx3 induces embryonic stem cell maturation to the midbrain dopamine neuron phenotype

Cecile Martinat, Jean-Jacques Bacci, Thomas Leete, Jongpil Kim, William B Vanti, Amy H Newman, Joo H Cha, Ulrik Gether, Honggang Wang, Asa Abeliovich

169 Citationer (Scopus)

Abstract

Midbrain dopamine (DA) neurons play a central role in the regulation of voluntary movement, and their degeneration is associated with Parkinson's disease. Cell replacement therapies, and in particular embryonic stem (ES) cell-derived DA neurons, offer a potential therapeutic venue for Parkinson's disease. We sought to identify genes that can potentiate maturation of ES cell cultures to the midbrain DA neuron phenotype. A number of transcription factors have been implicated in the development of midbrain DA neurons by expression analyses and loss-of-function knockout mouse studies, including Nurr1, Pitx3, Lmx1b, Engrailed-1, and Engrailed-2. However, none of these factors appear sufficient alone to induce the mature midbrain DA neuron phenotype in ES cell cultures in vitro, suggesting a more complex regulatory network. Here we show that Nurr1 and Pitx3 cooperatively promote terminal maturation to the midbrain DA neuron phenotype in murine and human ES cell cultures.

Originalsprog	Engelsk
Tidsskrift	Proceedings of the National Academy of Science of the United States of America
Vol/bind	103
Udgave nummer	8
Sider (fra-til)	2874-2879
Antal sider	6
ISSN	0027-8424
DOI	https://doi.org/10.1073/pnas.0511153103
Status	Udgivet - 2006

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10.1073/pnas.0511153103

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Martinat, C., Bacci, J-J., Leete, T., Kim, J., Vanti, W. B., Newman, A. H., Cha, J. H., Gether, U., Wang, H., & Abeliovich, A. (2006). Cooperative transcription activation by Nurr1 and Pitx3 induces embryonic stem cell maturation to the midbrain dopamine neuron phenotype. Proceedings of the National Academy of Science of the United States of America, 103(8), 2874-2879. https://doi.org/10.1073/pnas.0511153103

Cooperative transcription activation by Nurr1 and Pitx3 induces embryonic stem cell maturation to the midbrain dopamine neuron phenotype. / Martinat, Cecile; Bacci, Jean-Jacques; Leete, Thomas et al.

I: Proceedings of the National Academy of Science of the United States of America, Bind 103, Nr. 8, 2006, s. 2874-2879.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Martinat, C, Bacci, J-J, Leete, T, Kim, J, Vanti, WB, Newman, AH, Cha, JH, Gether, U, Wang, H & Abeliovich, A 2006, 'Cooperative transcription activation by Nurr1 and Pitx3 induces embryonic stem cell maturation to the midbrain dopamine neuron phenotype', Proceedings of the National Academy of Science of the United States of America, bind 103, nr. 8, s. 2874-2879. https://doi.org/10.1073/pnas.0511153103

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title = "Cooperative transcription activation by Nurr1 and Pitx3 induces embryonic stem cell maturation to the midbrain dopamine neuron phenotype",

abstract = "Midbrain dopamine (DA) neurons play a central role in the regulation of voluntary movement, and their degeneration is associated with Parkinson's disease. Cell replacement therapies, and in particular embryonic stem (ES) cell-derived DA neurons, offer a potential therapeutic venue for Parkinson's disease. We sought to identify genes that can potentiate maturation of ES cell cultures to the midbrain DA neuron phenotype. A number of transcription factors have been implicated in the development of midbrain DA neurons by expression analyses and loss-of-function knockout mouse studies, including Nurr1, Pitx3, Lmx1b, Engrailed-1, and Engrailed-2. However, none of these factors appear sufficient alone to induce the mature midbrain DA neuron phenotype in ES cell cultures in vitro, suggesting a more complex regulatory network. Here we show that Nurr1 and Pitx3 cooperatively promote terminal maturation to the midbrain DA neuron phenotype in murine and human ES cell cultures.",

keywords = "Animals, Cell Differentiation, Cells, Cultured, DNA-Binding Proteins, Dopamine, Embryo, Mammalian, Gene Expression Regulation, Developmental, Homeodomain Proteins, Humans, Mesencephalon, Mice, Neurons, Nuclear Receptor Subfamily 4, Group A, Member 2, Phenotype, Stem Cell Transplantation, Stem Cells, Transcription Factors",

author = "Cecile Martinat and Jean-Jacques Bacci and Thomas Leete and Jongpil Kim and Vanti, {William B} and Newman, {Amy H} and Cha, {Joo H} and Ulrik Gether and Honggang Wang and Asa Abeliovich",

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AU - Martinat, Cecile

AU - Bacci, Jean-Jacques

AU - Leete, Thomas

AU - Kim, Jongpil

AU - Vanti, William B

AU - Newman, Amy H

AU - Cha, Joo H

AU - Gether, Ulrik

AU - Wang, Honggang

AU - Abeliovich, Asa

PY - 2006

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N2 - Midbrain dopamine (DA) neurons play a central role in the regulation of voluntary movement, and their degeneration is associated with Parkinson's disease. Cell replacement therapies, and in particular embryonic stem (ES) cell-derived DA neurons, offer a potential therapeutic venue for Parkinson's disease. We sought to identify genes that can potentiate maturation of ES cell cultures to the midbrain DA neuron phenotype. A number of transcription factors have been implicated in the development of midbrain DA neurons by expression analyses and loss-of-function knockout mouse studies, including Nurr1, Pitx3, Lmx1b, Engrailed-1, and Engrailed-2. However, none of these factors appear sufficient alone to induce the mature midbrain DA neuron phenotype in ES cell cultures in vitro, suggesting a more complex regulatory network. Here we show that Nurr1 and Pitx3 cooperatively promote terminal maturation to the midbrain DA neuron phenotype in murine and human ES cell cultures.

AB - Midbrain dopamine (DA) neurons play a central role in the regulation of voluntary movement, and their degeneration is associated with Parkinson's disease. Cell replacement therapies, and in particular embryonic stem (ES) cell-derived DA neurons, offer a potential therapeutic venue for Parkinson's disease. We sought to identify genes that can potentiate maturation of ES cell cultures to the midbrain DA neuron phenotype. A number of transcription factors have been implicated in the development of midbrain DA neurons by expression analyses and loss-of-function knockout mouse studies, including Nurr1, Pitx3, Lmx1b, Engrailed-1, and Engrailed-2. However, none of these factors appear sufficient alone to induce the mature midbrain DA neuron phenotype in ES cell cultures in vitro, suggesting a more complex regulatory network. Here we show that Nurr1 and Pitx3 cooperatively promote terminal maturation to the midbrain DA neuron phenotype in murine and human ES cell cultures.

KW - Animals

KW - Cell Differentiation

KW - Cells, Cultured

KW - DNA-Binding Proteins

KW - Dopamine

KW - Embryo, Mammalian

KW - Gene Expression Regulation, Developmental

KW - Homeodomain Proteins

KW - Humans

KW - Mesencephalon

KW - Mice

KW - Neurons

KW - Nuclear Receptor Subfamily 4, Group A, Member 2

KW - Phenotype

KW - Stem Cell Transplantation

KW - Stem Cells

KW - Transcription Factors

U2 - 10.1073/pnas.0511153103

DO - 10.1073/pnas.0511153103

M3 - Journal article

C2 - 16477036

SN - 0027-8424

VL - 103

SP - 2874

EP - 2879

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 8

ER -

Cooperative transcription activation by Nurr1 and Pitx3 induces embryonic stem cell maturation to the midbrain dopamine neuron phenotype

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