Absence of Both Thyroid Hormone Transporters MCT8 and OATP1C1 Impairs Neural Stem Cell Fate in the Adult Mouse Subventricular Zone

Cristina Luongo; Lucile Butruille; Anthony Sébillot; Karine Le Blay; Markus Schwaninger; Heike Heuer; Barbara A. Demeneix; Sylvie Remaud

doi:10.1016/j.stemcr.2020.12.009

Absence of Both Thyroid Hormone Transporters MCT8 and OATP1C1 Impairs Neural Stem Cell Fate in the Adult Mouse Subventricular Zone

Cristina Luongo, Lucile Butruille, Anthony Sébillot, Karine Le Blay, Markus Schwaninger, Heike Heuer, Barbara A. Demeneix, Sylvie Remaud^*

^*Corresponding author for this work

Institute of Experimental and Clinical Pharmacology and Toxicology

25 Citations (Scopus)

Abstract

Adult neural stem cell (NSC) generation in vertebrate brains requires thyroid hormones (THs). How THs enter the NSC population is unknown, although TH availability determines proliferation and neuronal versus glial progenitor determination in murine subventricular zone (SVZ) NSCs. Mice display neurological signs of the severely disabling human disease, Allan-Herndon-Dudley syndrome, if they lack both MCT8 and OATP1C1 transporters, or MCT8 and deiodinase type 2. We analyzed the distribution of MCT8 and OATP1C1 in adult mouse SVZ. Both are strongly expressed in NSCs and at a lower level in neuronal cell precursors but not in oligodendrocyte progenitors. Next, we analyzed Mct8/Oatp1c1 double-knockout mice, where brain uptake of THs is strongly reduced. NSC proliferation and determination to neuronal fates were severely affected, but not SVZ-oligodendroglial progenitor generation. This work highlights how tight control of TH availability determines NSC function and glial-neuron cell-fate choice in adult brains.

Original language	English
Journal	Stem Cell Reports
Volume	16
Issue number	2
Pages (from-to)	337-353
Number of pages	17
ISSN	2213-6711
DOIs	https://doi.org/10.1016/j.stemcr.2020.12.009
Publication status	Published - 09.02.2021

Funding

The authors would like to thank S. Sosinsky and F. Uridat for the excellent animal care. We also thank the ImagoSeine platform of the Institute Jacques Monod, Université René Descartes for the imaging advice. This work was supported by the CNRS and the EU H2020 contract Thyrage (grant n° 666869 ). H.H. and M.S. are supported by the Deutsche Forschungsgemeinschaft (DFG; TR 296/1-P01 ).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

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10.1016/j.stemcr.2020.12.009

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title = "Absence of Both Thyroid Hormone Transporters MCT8 and OATP1C1 Impairs Neural Stem Cell Fate in the Adult Mouse Subventricular Zone",

abstract = "Adult neural stem cell (NSC) generation in vertebrate brains requires thyroid hormones (THs). How THs enter the NSC population is unknown, although TH availability determines proliferation and neuronal versus glial progenitor determination in murine subventricular zone (SVZ) NSCs. Mice display neurological signs of the severely disabling human disease, Allan-Herndon-Dudley syndrome, if they lack both MCT8 and OATP1C1 transporters, or MCT8 and deiodinase type 2. We analyzed the distribution of MCT8 and OATP1C1 in adult mouse SVZ. Both are strongly expressed in NSCs and at a lower level in neuronal cell precursors but not in oligodendrocyte progenitors. Next, we analyzed Mct8/Oatp1c1 double-knockout mice, where brain uptake of THs is strongly reduced. NSC proliferation and determination to neuronal fates were severely affected, but not SVZ-oligodendroglial progenitor generation. This work highlights how tight control of TH availability determines NSC function and glial-neuron cell-fate choice in adult brains.",

author = "Cristina Luongo and Lucile Butruille and Anthony S{\'e}billot and \{Le Blay\}, Karine and Markus Schwaninger and Heike Heuer and Demeneix, \{Barbara A.\} and Sylvie Remaud",

note = "Funding Information: The authors would like to thank S. Sosinsky and F. Uridat for the excellent animal care. We also thank the ImagoSeine platform of the Institute Jacques Monod, Universit{\'e} Ren{\'e} Descartes for the imaging advice. This work was supported by the CNRS and the EU H2020 contract Thyrage (grant n° 666869 ). H.H. and M.S. are supported by the Deutsche Forschungsgemeinschaft (DFG; TR 296/1-P01 ). Publisher Copyright: {\textcopyright} 2020 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

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doi = "10.1016/j.stemcr.2020.12.009",

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AU - Luongo, Cristina

AU - Butruille, Lucile

AU - Sébillot, Anthony

AU - Le Blay, Karine

AU - Schwaninger, Markus

AU - Heuer, Heike

AU - Demeneix, Barbara A.

AU - Remaud, Sylvie

N1 - Funding Information: The authors would like to thank S. Sosinsky and F. Uridat for the excellent animal care. We also thank the ImagoSeine platform of the Institute Jacques Monod, Université René Descartes for the imaging advice. This work was supported by the CNRS and the EU H2020 contract Thyrage (grant n° 666869 ). H.H. and M.S. are supported by the Deutsche Forschungsgemeinschaft (DFG; TR 296/1-P01 ). Publisher Copyright: © 2020 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/2/9

Y1 - 2021/2/9

N2 - Adult neural stem cell (NSC) generation in vertebrate brains requires thyroid hormones (THs). How THs enter the NSC population is unknown, although TH availability determines proliferation and neuronal versus glial progenitor determination in murine subventricular zone (SVZ) NSCs. Mice display neurological signs of the severely disabling human disease, Allan-Herndon-Dudley syndrome, if they lack both MCT8 and OATP1C1 transporters, or MCT8 and deiodinase type 2. We analyzed the distribution of MCT8 and OATP1C1 in adult mouse SVZ. Both are strongly expressed in NSCs and at a lower level in neuronal cell precursors but not in oligodendrocyte progenitors. Next, we analyzed Mct8/Oatp1c1 double-knockout mice, where brain uptake of THs is strongly reduced. NSC proliferation and determination to neuronal fates were severely affected, but not SVZ-oligodendroglial progenitor generation. This work highlights how tight control of TH availability determines NSC function and glial-neuron cell-fate choice in adult brains.

AB - Adult neural stem cell (NSC) generation in vertebrate brains requires thyroid hormones (THs). How THs enter the NSC population is unknown, although TH availability determines proliferation and neuronal versus glial progenitor determination in murine subventricular zone (SVZ) NSCs. Mice display neurological signs of the severely disabling human disease, Allan-Herndon-Dudley syndrome, if they lack both MCT8 and OATP1C1 transporters, or MCT8 and deiodinase type 2. We analyzed the distribution of MCT8 and OATP1C1 in adult mouse SVZ. Both are strongly expressed in NSCs and at a lower level in neuronal cell precursors but not in oligodendrocyte progenitors. Next, we analyzed Mct8/Oatp1c1 double-knockout mice, where brain uptake of THs is strongly reduced. NSC proliferation and determination to neuronal fates were severely affected, but not SVZ-oligodendroglial progenitor generation. This work highlights how tight control of TH availability determines NSC function and glial-neuron cell-fate choice in adult brains.

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Absence of Both Thyroid Hormone Transporters MCT8 and OATP1C1 Impairs Neural Stem Cell Fate in the Adult Mouse Subventricular Zone

Abstract

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