Inborn Errors of Long-Chain Fatty Acid β-Oxidation Link Neural Stem Cell Self-Renewal to Autism
Summary: Inborn errors of metabolism (IEMs) occur with high incidence in human populations. Especially prevalent among these are inborn deficiencies in fatty acid β-oxidation (FAO), which are clinically associated with developmental neuropsychiatric disorders, including autism. We now report that ne...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-02-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716000085 |
| _version_ | 1818062205477715968 |
|---|---|
| author | Zhigang Xie Albert Jones Jude T. Deeney Seong Kwon Hur Vytas A. Bankaitis |
| author_facet | Zhigang Xie Albert Jones Jude T. Deeney Seong Kwon Hur Vytas A. Bankaitis |
| author_sort | Zhigang Xie |
| collection | DOAJ |
| description | Summary: Inborn errors of metabolism (IEMs) occur with high incidence in human populations. Especially prevalent among these are inborn deficiencies in fatty acid β-oxidation (FAO), which are clinically associated with developmental neuropsychiatric disorders, including autism. We now report that neural stem cell (NSC)-autonomous insufficiencies in the activity of TMLHE (an autism risk factor that supports long-chain FAO by catalyzing carnitine biosynthesis), of CPT1A (an enzyme required for long-chain FAO transport into mitochondria), or of fatty acid mobilization from lipid droplets reduced NSC pools in the mouse embryonic neocortex. Lineage tracing experiments demonstrated that reduced flux through the FAO pathway potentiated NSC symmetric differentiating divisions at the expense of self-renewing stem cell division modes. The collective data reveal a key role for FAO in controlling NSC-to-IPC transition in the mammalian embryonic brain and suggest NSC self renewal as a cellular mechanism underlying the association between IEMs and autism. : The mechanisms underlying the association between inborn errors of fatty acid metabolism and developmental brain disorders such as autism remain unclear. Xie et al. find that TMLHE, a carnitine biosynthesis enzyme, and carnitine-dependent long-chain fatty acid β-oxidation control the neural stem cell pool during neocortical development by maintaining self-renewing divisions. |
| first_indexed | 2024-12-10T14:00:30Z |
| format | Article |
| id | doaj.art-677d4391706e432687a66dd2704b9214 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T14:00:30Z |
| publishDate | 2016-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-677d4391706e432687a66dd2704b92142022-12-22T01:45:49ZengElsevierCell Reports2211-12472016-02-01145991999Inborn Errors of Long-Chain Fatty Acid β-Oxidation Link Neural Stem Cell Self-Renewal to AutismZhigang Xie0Albert Jones1Jude T. Deeney2Seong Kwon Hur3Vytas A. Bankaitis4Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, College Station, TX 77843, USA; Corresponding authorDepartment of Medicine, Obesity Research Center, Boston University School of Medicine, Boston, MA 02118, USADepartment of Medicine, Obesity Research Center, Boston University School of Medicine, Boston, MA 02118, USADepartment of Molecular and Cellular Medicine, Texas A&M University Health Science Center, College Station, TX 77843, USADepartment of Molecular and Cellular Medicine, Texas A&M University Health Science Center, College Station, TX 77843, USASummary: Inborn errors of metabolism (IEMs) occur with high incidence in human populations. Especially prevalent among these are inborn deficiencies in fatty acid β-oxidation (FAO), which are clinically associated with developmental neuropsychiatric disorders, including autism. We now report that neural stem cell (NSC)-autonomous insufficiencies in the activity of TMLHE (an autism risk factor that supports long-chain FAO by catalyzing carnitine biosynthesis), of CPT1A (an enzyme required for long-chain FAO transport into mitochondria), or of fatty acid mobilization from lipid droplets reduced NSC pools in the mouse embryonic neocortex. Lineage tracing experiments demonstrated that reduced flux through the FAO pathway potentiated NSC symmetric differentiating divisions at the expense of self-renewing stem cell division modes. The collective data reveal a key role for FAO in controlling NSC-to-IPC transition in the mammalian embryonic brain and suggest NSC self renewal as a cellular mechanism underlying the association between IEMs and autism. : The mechanisms underlying the association between inborn errors of fatty acid metabolism and developmental brain disorders such as autism remain unclear. Xie et al. find that TMLHE, a carnitine biosynthesis enzyme, and carnitine-dependent long-chain fatty acid β-oxidation control the neural stem cell pool during neocortical development by maintaining self-renewing divisions.http://www.sciencedirect.com/science/article/pii/S2211124716000085 |
| spellingShingle | Zhigang Xie Albert Jones Jude T. Deeney Seong Kwon Hur Vytas A. Bankaitis Inborn Errors of Long-Chain Fatty Acid β-Oxidation Link Neural Stem Cell Self-Renewal to Autism Cell Reports |
| title | Inborn Errors of Long-Chain Fatty Acid β-Oxidation Link Neural Stem Cell Self-Renewal to Autism |
| title_full | Inborn Errors of Long-Chain Fatty Acid β-Oxidation Link Neural Stem Cell Self-Renewal to Autism |
| title_fullStr | Inborn Errors of Long-Chain Fatty Acid β-Oxidation Link Neural Stem Cell Self-Renewal to Autism |
| title_full_unstemmed | Inborn Errors of Long-Chain Fatty Acid β-Oxidation Link Neural Stem Cell Self-Renewal to Autism |
| title_short | Inborn Errors of Long-Chain Fatty Acid β-Oxidation Link Neural Stem Cell Self-Renewal to Autism |
| title_sort | inborn errors of long chain fatty acid β oxidation link neural stem cell self renewal to autism |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716000085 |
| work_keys_str_mv | AT zhigangxie inbornerrorsoflongchainfattyacidboxidationlinkneuralstemcellselfrenewaltoautism AT albertjones inbornerrorsoflongchainfattyacidboxidationlinkneuralstemcellselfrenewaltoautism AT judetdeeney inbornerrorsoflongchainfattyacidboxidationlinkneuralstemcellselfrenewaltoautism AT seongkwonhur inbornerrorsoflongchainfattyacidboxidationlinkneuralstemcellselfrenewaltoautism AT vytasabankaitis inbornerrorsoflongchainfattyacidboxidationlinkneuralstemcellselfrenewaltoautism |