Overcoming monocarboxylate transporter 8 (MCT8)-deficiency to promote human oligodendrocyte differentiation and myelination
Cell membrane thyroid hormone (TH) transport can be facilitated by the monocarboxylate transporter 8 (MCT8), encoded by the solute carrier family 16 member 2 (SLC16A2) gene. Human mutations of the gene, SLC16A2, result in the X-linked-inherited psychomotor retardation and hypomyelination disorder, A...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Elsevier
2017
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| _version_ | 1826305132852150272 |
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| author | Lee, JY Kim, MJ Deliyanti, D Azari, MF Rossello, F Costin, A Ramm, G Stanley, EG Elefanty, AG Wilkinson-Berka, JL Petratos, S |
| author_facet | Lee, JY Kim, MJ Deliyanti, D Azari, MF Rossello, F Costin, A Ramm, G Stanley, EG Elefanty, AG Wilkinson-Berka, JL Petratos, S |
| author_sort | Lee, JY |
| collection | OXFORD |
| description | Cell membrane thyroid hormone (TH) transport can be facilitated by the monocarboxylate transporter 8 (MCT8), encoded by the solute carrier family 16 member 2 (SLC16A2) gene. Human mutations of the gene, SLC16A2, result in the X-linked-inherited psychomotor retardation and hypomyelination disorder, Allan-Herndon-Dudley syndrome (AHDS). We posited that abrogating MCT8-dependent TH transport limits oligodendrogenesis and myelination. We show that human oligodendrocytes (OL), derived from the NKX2.1-GFP human embryonic stem cell (hESC) reporter line, express MCT8. Moreover, treatment of these cultures with DITPA (an MCT8-independent TH analog), up-regulates OL differentiation transcription factors and myelin gene expression. DITPA promotes hESC-derived OL myelination of retinal ganglion axons in co-culture. Pharmacological and genetic blockade of MCT8 induces significant OL apoptosis, impairing myelination. DITPA treatment limits OL apoptosis mediated by SLC16A2 down-regulation primarily signaling through AKT phosphorylation, driving myelination. Our results highlight the potential role of MCT8 in TH transport for human OL development and may implicate DITPA as a promising treatment for developmentally-regulated myelination in AHDS. |
| first_indexed | 2024-03-07T06:28:14Z |
| format | Journal article |
| id | oxford-uuid:f51048eb-e874-4d67-9393-0dfc96f0ecd0 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:28:14Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:f51048eb-e874-4d67-9393-0dfc96f0ecd02022-03-27T12:24:32ZOvercoming monocarboxylate transporter 8 (MCT8)-deficiency to promote human oligodendrocyte differentiation and myelinationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f51048eb-e874-4d67-9393-0dfc96f0ecd0EnglishSymplectic Elements at OxfordElsevier2017Lee, JYKim, MJDeliyanti, DAzari, MFRossello, FCostin, ARamm, GStanley, EGElefanty, AGWilkinson-Berka, JLPetratos, SCell membrane thyroid hormone (TH) transport can be facilitated by the monocarboxylate transporter 8 (MCT8), encoded by the solute carrier family 16 member 2 (SLC16A2) gene. Human mutations of the gene, SLC16A2, result in the X-linked-inherited psychomotor retardation and hypomyelination disorder, Allan-Herndon-Dudley syndrome (AHDS). We posited that abrogating MCT8-dependent TH transport limits oligodendrogenesis and myelination. We show that human oligodendrocytes (OL), derived from the NKX2.1-GFP human embryonic stem cell (hESC) reporter line, express MCT8. Moreover, treatment of these cultures with DITPA (an MCT8-independent TH analog), up-regulates OL differentiation transcription factors and myelin gene expression. DITPA promotes hESC-derived OL myelination of retinal ganglion axons in co-culture. Pharmacological and genetic blockade of MCT8 induces significant OL apoptosis, impairing myelination. DITPA treatment limits OL apoptosis mediated by SLC16A2 down-regulation primarily signaling through AKT phosphorylation, driving myelination. Our results highlight the potential role of MCT8 in TH transport for human OL development and may implicate DITPA as a promising treatment for developmentally-regulated myelination in AHDS. |
| spellingShingle | Lee, JY Kim, MJ Deliyanti, D Azari, MF Rossello, F Costin, A Ramm, G Stanley, EG Elefanty, AG Wilkinson-Berka, JL Petratos, S Overcoming monocarboxylate transporter 8 (MCT8)-deficiency to promote human oligodendrocyte differentiation and myelination |
| title | Overcoming monocarboxylate transporter 8 (MCT8)-deficiency to promote human oligodendrocyte differentiation and myelination |
| title_full | Overcoming monocarboxylate transporter 8 (MCT8)-deficiency to promote human oligodendrocyte differentiation and myelination |
| title_fullStr | Overcoming monocarboxylate transporter 8 (MCT8)-deficiency to promote human oligodendrocyte differentiation and myelination |
| title_full_unstemmed | Overcoming monocarboxylate transporter 8 (MCT8)-deficiency to promote human oligodendrocyte differentiation and myelination |
| title_short | Overcoming monocarboxylate transporter 8 (MCT8)-deficiency to promote human oligodendrocyte differentiation and myelination |
| title_sort | overcoming monocarboxylate transporter 8 mct8 deficiency to promote human oligodendrocyte differentiation and myelination |
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