COUP-TF1 Modulates Thyroid Hormone Action in an Embryonic Stem-Cell Model of Cortical Pyramidal Neuronal Differentiation

Background: Thyroid hormone is critical for normal brain development and acts in a spatial and temporal specific pattern. Thyroid hormone excess, or deficiency, can lead to irreversible impairment of brain and sensory development. Chicken ovalbumin upstream-transcription factor 1 (COUP-TF1), express...

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Veröffentlicht in:Thyroid (New York, N.Y.) N.Y.), 2018-05, Vol.28 (5), p.667-678
Hauptverfasser: Teng, Xiaochun, Liu, Yan-Yun, Teng, Weiping, Brent, Gregory A.
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container_title Thyroid (New York, N.Y.)
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creator Teng, Xiaochun
Liu, Yan-Yun
Teng, Weiping
Brent, Gregory A.
description Background: Thyroid hormone is critical for normal brain development and acts in a spatial and temporal specific pattern. Thyroid hormone excess, or deficiency, can lead to irreversible impairment of brain and sensory development. Chicken ovalbumin upstream-transcription factor 1 (COUP-TF1), expressed early in neuronal development, is essential to achieve normal brain structure. Thyroid hormone stimulation of gene expression is inversely correlated with the level of COUP-TF1 expression. Methods: An in vitro method of differentiating mouse embryonic stem (mES) cells into cortical neurons was utilized to study the influence of COUP-TF1 on thyroid hormone signaling in brain development. mES cells were cultured and differentiated in specific conditioned media, and a high percentage of nestin-positive progenitor neurons in the first stage, and cortical neurons in the second stage, was obtained with characteristic neuronal firing. Results: The number of nestin-positive progenitors, as determined by fluorescence-activated cell sorting analysis, was significantly greater with triiodothyronine (T3) treatment compared to control ( p  
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Thyroid hormone excess, or deficiency, can lead to irreversible impairment of brain and sensory development. Chicken ovalbumin upstream-transcription factor 1 (COUP-TF1), expressed early in neuronal development, is essential to achieve normal brain structure. Thyroid hormone stimulation of gene expression is inversely correlated with the level of COUP-TF1 expression. Methods: An in vitro method of differentiating mouse embryonic stem (mES) cells into cortical neurons was utilized to study the influence of COUP-TF1 on thyroid hormone signaling in brain development. mES cells were cultured and differentiated in specific conditioned media, and a high percentage of nestin-positive progenitor neurons in the first stage, and cortical neurons in the second stage, was obtained with characteristic neuronal firing. Results: The number of nestin-positive progenitors, as determined by fluorescence-activated cell sorting analysis, was significantly greater with triiodothyronine (T3) treatment compared to control ( p  &lt; 0.05). T3 enhanced the expression of cortical neuron marker (Tbr1 and Rc3) mRNAs. After COUP-TF1 knockdown, the number of nestin-positive progenitors was reduced compared to control ( p  &lt; 0.05), but the number increased with T3 treatment. The mRNA of cortical neuronal gene markers was measured after COUP-TF1 knockdown. In the presence of T3, the peak expression of neuron markers Emx1, Tbr1, Camkiv, and Rc3 mRNA was earlier, at day 18 of differentiation, compared to control cells, at day 22. Furthermore, after COUP-TF1 knockdown, T3 induction of Rc3 and Tbr1 mRNA was significantly enhanced compared to cells expressing COUP-TF1. Conclusion: These results indicate that COUP-TF1 plays an important role in modulating the timing and magnitude of T3-stimulated gene expression required for normal corticogenesis.</description><identifier>ISSN: 1050-7256</identifier><identifier>EISSN: 1557-9077</identifier><identifier>DOI: 10.1089/thy.2017.0256</identifier><identifier>PMID: 29205104</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Animals ; Cell Proliferation - drug effects ; Cell Proliferation - physiology ; Cell Survival - drug effects ; Cell Survival - physiology ; COUP Transcription Factor I - genetics ; COUP Transcription Factor I - metabolism ; Embryonic Stem Cells - cytology ; Embryonic Stem Cells - drug effects ; Embryonic Stem Cells - metabolism ; Gene Expression - drug effects ; Gene Expression - physiology ; Mice ; Nestin - metabolism ; Neurogenesis - drug effects ; Neurogenesis - physiology ; Pyramidal Cells - cytology ; Pyramidal Cells - drug effects ; Pyramidal Cells - metabolism ; Thyroid Economy: Regulation, Cell Biology, and Thyroid Hormone Metabolism and Action ; Triiodothyronine - pharmacology ; Vesicular Glutamate Transport Protein 1 - metabolism</subject><ispartof>Thyroid (New York, N.Y.), 2018-05, Vol.28 (5), p.667-678</ispartof><rights>2018, Mary Ann Liebert, Inc.</rights><rights>Copyright 2018, Mary Ann Liebert, Inc. 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c431t-33e6192fb5b64f7ec3a2cfcc5793a84d1ab434af277a023bb2a77a1d2f11db853</citedby><cites>FETCH-LOGICAL-c431t-33e6192fb5b64f7ec3a2cfcc5793a84d1ab434af277a023bb2a77a1d2f11db853</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29205104$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Teng, Xiaochun</creatorcontrib><creatorcontrib>Liu, Yan-Yun</creatorcontrib><creatorcontrib>Teng, Weiping</creatorcontrib><creatorcontrib>Brent, Gregory A.</creatorcontrib><title>COUP-TF1 Modulates Thyroid Hormone Action in an Embryonic Stem-Cell Model of Cortical Pyramidal Neuronal Differentiation</title><title>Thyroid (New York, N.Y.)</title><addtitle>Thyroid</addtitle><description>Background: Thyroid hormone is critical for normal brain development and acts in a spatial and temporal specific pattern. Thyroid hormone excess, or deficiency, can lead to irreversible impairment of brain and sensory development. Chicken ovalbumin upstream-transcription factor 1 (COUP-TF1), expressed early in neuronal development, is essential to achieve normal brain structure. Thyroid hormone stimulation of gene expression is inversely correlated with the level of COUP-TF1 expression. Methods: An in vitro method of differentiating mouse embryonic stem (mES) cells into cortical neurons was utilized to study the influence of COUP-TF1 on thyroid hormone signaling in brain development. mES cells were cultured and differentiated in specific conditioned media, and a high percentage of nestin-positive progenitor neurons in the first stage, and cortical neurons in the second stage, was obtained with characteristic neuronal firing. Results: The number of nestin-positive progenitors, as determined by fluorescence-activated cell sorting analysis, was significantly greater with triiodothyronine (T3) treatment compared to control ( p  &lt; 0.05). T3 enhanced the expression of cortical neuron marker (Tbr1 and Rc3) mRNAs. After COUP-TF1 knockdown, the number of nestin-positive progenitors was reduced compared to control ( p  &lt; 0.05), but the number increased with T3 treatment. The mRNA of cortical neuronal gene markers was measured after COUP-TF1 knockdown. In the presence of T3, the peak expression of neuron markers Emx1, Tbr1, Camkiv, and Rc3 mRNA was earlier, at day 18 of differentiation, compared to control cells, at day 22. Furthermore, after COUP-TF1 knockdown, T3 induction of Rc3 and Tbr1 mRNA was significantly enhanced compared to cells expressing COUP-TF1. Conclusion: These results indicate that COUP-TF1 plays an important role in modulating the timing and magnitude of T3-stimulated gene expression required for normal corticogenesis.</description><subject>Animals</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Proliferation - physiology</subject><subject>Cell Survival - drug effects</subject><subject>Cell Survival - physiology</subject><subject>COUP Transcription Factor I - genetics</subject><subject>COUP Transcription Factor I - metabolism</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Embryonic Stem Cells - drug effects</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>Gene Expression - drug effects</subject><subject>Gene Expression - physiology</subject><subject>Mice</subject><subject>Nestin - metabolism</subject><subject>Neurogenesis - drug effects</subject><subject>Neurogenesis - physiology</subject><subject>Pyramidal Cells - cytology</subject><subject>Pyramidal Cells - drug effects</subject><subject>Pyramidal Cells - metabolism</subject><subject>Thyroid Economy: Regulation, Cell Biology, and Thyroid Hormone Metabolism and Action</subject><subject>Triiodothyronine - pharmacology</subject><subject>Vesicular Glutamate Transport Protein 1 - metabolism</subject><issn>1050-7256</issn><issn>1557-9077</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctOwzAQRS0EoryWbJF_IMWPuG42SFV4SkAr0a4t27GpUWJXTorI3-OogGDFaq7Gd85YcwE4x2iM0bS47Nb9mCDMx4iwyR44wozxrECc7yeNGMp46o_Acdu-IYQnU04PwYgUBDGM8iPwUc5Xi2x5i-FTqLa17EwLl-s-BlfB-xCb4A2c6c4FD52H0sObRsU-eKfhS2earDR1PYyaGgYLyxA7p2UNF32UjauSejbbGHwS185aE43vnBxwp-DAyro1Z1_1BKxub5blffY4v3soZ4-ZzinuMkrNBBfEKqYmueVGU0m01ZrxgsppXmGpcppLSziXiFCliEwKV8RiXKkpoyfgasfdbFVjKp0-EGUtNtE1MvYiSCf-vni3Fq_hXbCCEZqjBMh2AB1D20Zjf2YxEkMEIkUghgjEEEHyX_xe-OP-vnky0J1haEvva2eUid0_2E_R6JYa</recordid><startdate>20180501</startdate><enddate>20180501</enddate><creator>Teng, Xiaochun</creator><creator>Liu, Yan-Yun</creator><creator>Teng, Weiping</creator><creator>Brent, Gregory A.</creator><general>Mary Ann Liebert, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20180501</creationdate><title>COUP-TF1 Modulates Thyroid Hormone Action in an Embryonic Stem-Cell Model of Cortical Pyramidal Neuronal Differentiation</title><author>Teng, Xiaochun ; Liu, Yan-Yun ; Teng, Weiping ; Brent, Gregory A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c431t-33e6192fb5b64f7ec3a2cfcc5793a84d1ab434af277a023bb2a77a1d2f11db853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Proliferation - physiology</topic><topic>Cell Survival - drug effects</topic><topic>Cell Survival - physiology</topic><topic>COUP Transcription Factor I - genetics</topic><topic>COUP Transcription Factor I - metabolism</topic><topic>Embryonic Stem Cells - cytology</topic><topic>Embryonic Stem Cells - drug effects</topic><topic>Embryonic Stem Cells - metabolism</topic><topic>Gene Expression - drug effects</topic><topic>Gene Expression - physiology</topic><topic>Mice</topic><topic>Nestin - metabolism</topic><topic>Neurogenesis - drug effects</topic><topic>Neurogenesis - physiology</topic><topic>Pyramidal Cells - cytology</topic><topic>Pyramidal Cells - drug effects</topic><topic>Pyramidal Cells - metabolism</topic><topic>Thyroid Economy: Regulation, Cell Biology, and Thyroid Hormone Metabolism and Action</topic><topic>Triiodothyronine - pharmacology</topic><topic>Vesicular Glutamate Transport Protein 1 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Teng, Xiaochun</creatorcontrib><creatorcontrib>Liu, Yan-Yun</creatorcontrib><creatorcontrib>Teng, Weiping</creatorcontrib><creatorcontrib>Brent, Gregory A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Thyroid (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Teng, Xiaochun</au><au>Liu, Yan-Yun</au><au>Teng, Weiping</au><au>Brent, Gregory A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>COUP-TF1 Modulates Thyroid Hormone Action in an Embryonic Stem-Cell Model of Cortical Pyramidal Neuronal Differentiation</atitle><jtitle>Thyroid (New York, N.Y.)</jtitle><addtitle>Thyroid</addtitle><date>2018-05-01</date><risdate>2018</risdate><volume>28</volume><issue>5</issue><spage>667</spage><epage>678</epage><pages>667-678</pages><issn>1050-7256</issn><eissn>1557-9077</eissn><abstract>Background: Thyroid hormone is critical for normal brain development and acts in a spatial and temporal specific pattern. Thyroid hormone excess, or deficiency, can lead to irreversible impairment of brain and sensory development. Chicken ovalbumin upstream-transcription factor 1 (COUP-TF1), expressed early in neuronal development, is essential to achieve normal brain structure. Thyroid hormone stimulation of gene expression is inversely correlated with the level of COUP-TF1 expression. Methods: An in vitro method of differentiating mouse embryonic stem (mES) cells into cortical neurons was utilized to study the influence of COUP-TF1 on thyroid hormone signaling in brain development. mES cells were cultured and differentiated in specific conditioned media, and a high percentage of nestin-positive progenitor neurons in the first stage, and cortical neurons in the second stage, was obtained with characteristic neuronal firing. Results: The number of nestin-positive progenitors, as determined by fluorescence-activated cell sorting analysis, was significantly greater with triiodothyronine (T3) treatment compared to control ( p  &lt; 0.05). T3 enhanced the expression of cortical neuron marker (Tbr1 and Rc3) mRNAs. After COUP-TF1 knockdown, the number of nestin-positive progenitors was reduced compared to control ( p  &lt; 0.05), but the number increased with T3 treatment. The mRNA of cortical neuronal gene markers was measured after COUP-TF1 knockdown. In the presence of T3, the peak expression of neuron markers Emx1, Tbr1, Camkiv, and Rc3 mRNA was earlier, at day 18 of differentiation, compared to control cells, at day 22. Furthermore, after COUP-TF1 knockdown, T3 induction of Rc3 and Tbr1 mRNA was significantly enhanced compared to cells expressing COUP-TF1. Conclusion: These results indicate that COUP-TF1 plays an important role in modulating the timing and magnitude of T3-stimulated gene expression required for normal corticogenesis.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>29205104</pmid><doi>10.1089/thy.2017.0256</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record>
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subjects Animals
Cell Proliferation - drug effects
Cell Proliferation - physiology
Cell Survival - drug effects
Cell Survival - physiology
COUP Transcription Factor I - genetics
COUP Transcription Factor I - metabolism
Embryonic Stem Cells - cytology
Embryonic Stem Cells - drug effects
Embryonic Stem Cells - metabolism
Gene Expression - drug effects
Gene Expression - physiology
Mice
Nestin - metabolism
Neurogenesis - drug effects
Neurogenesis - physiology
Pyramidal Cells - cytology
Pyramidal Cells - drug effects
Pyramidal Cells - metabolism
Thyroid Economy: Regulation, Cell Biology, and Thyroid Hormone Metabolism and Action
Triiodothyronine - pharmacology
Vesicular Glutamate Transport Protein 1 - metabolism
title COUP-TF1 Modulates Thyroid Hormone Action in an Embryonic Stem-Cell Model of Cortical Pyramidal Neuronal Differentiation
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