16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis
The complex 16p11.2 deletion syndrome (16pdel) is accompanied by neurological disorders, including epilepsy, autism spectrum disorder, and intellectual disability. We demonstrated that 16pdel iPSC differentiated neurons from affected people show augmented local field potential activity and altered c...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier BV
2022
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| Online Access: | https://hdl.handle.net/1721.1/146841 |
| _version_ | 1826204020203585536 |
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| author | Tomasello, Danielle L Kim, Jiyoon L Khodour, Yara McCammon, Jasmine M Mitalipova, Maya Jaenisch, Rudolf Futerman, Anthony H Sive, Hazel |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Tomasello, Danielle L Kim, Jiyoon L Khodour, Yara McCammon, Jasmine M Mitalipova, Maya Jaenisch, Rudolf Futerman, Anthony H Sive, Hazel |
| author_sort | Tomasello, Danielle L |
| collection | MIT |
| description | The complex 16p11.2 deletion syndrome (16pdel) is accompanied by neurological disorders, including epilepsy, autism spectrum disorder, and intellectual disability. We demonstrated that 16pdel iPSC differentiated neurons from affected people show augmented local field potential activity and altered ceramide-related lipid species relative to unaffected. FAM57B, a poorly characterized gene in the 16p11.2 interval, has emerged as a candidate tied to symptomatology. We found that FAM57B modulates ceramide synthase (CerS) activity, but is not a CerS per se. In FAM57B mutant human neuronal cells and zebrafish brain, composition and levels of sphingolipids and glycerolipids associated with cellular membranes are disrupted. Consistently, we observed aberrant plasma membrane architecture and synaptic protein mislocalization, which were accompanied by depressed brain and behavioral activity. Together, these results suggest that haploinsufficiency of FAM57B contributes to changes in neuronal activity and function in 16pdel syndrome through a crucial role for the gene in lipid metabolism. |
| first_indexed | 2024-09-23T12:47:34Z |
| format | Article |
| id | mit-1721.1/146841 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T12:47:34Z |
| publishDate | 2022 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1468412022-12-13T03:24:31Z 16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis Tomasello, Danielle L Kim, Jiyoon L Khodour, Yara McCammon, Jasmine M Mitalipova, Maya Jaenisch, Rudolf Futerman, Anthony H Sive, Hazel Massachusetts Institute of Technology. Department of Biology The complex 16p11.2 deletion syndrome (16pdel) is accompanied by neurological disorders, including epilepsy, autism spectrum disorder, and intellectual disability. We demonstrated that 16pdel iPSC differentiated neurons from affected people show augmented local field potential activity and altered ceramide-related lipid species relative to unaffected. FAM57B, a poorly characterized gene in the 16p11.2 interval, has emerged as a candidate tied to symptomatology. We found that FAM57B modulates ceramide synthase (CerS) activity, but is not a CerS per se. In FAM57B mutant human neuronal cells and zebrafish brain, composition and levels of sphingolipids and glycerolipids associated with cellular membranes are disrupted. Consistently, we observed aberrant plasma membrane architecture and synaptic protein mislocalization, which were accompanied by depressed brain and behavioral activity. Together, these results suggest that haploinsufficiency of FAM57B contributes to changes in neuronal activity and function in 16pdel syndrome through a crucial role for the gene in lipid metabolism. 2022-12-12T14:54:31Z 2022-12-12T14:54:31Z 2022 2022-12-12T14:43:55Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/146841 Tomasello, Danielle L, Kim, Jiyoon L, Khodour, Yara, McCammon, Jasmine M, Mitalipova, Maya et al. 2022. "16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis." iScience, 25 (1). en 10.1016/J.ISCI.2021.103551 iScience Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV Elsevier |
| spellingShingle | Tomasello, Danielle L Kim, Jiyoon L Khodour, Yara McCammon, Jasmine M Mitalipova, Maya Jaenisch, Rudolf Futerman, Anthony H Sive, Hazel 16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis |
| title | 16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis |
| title_full | 16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis |
| title_fullStr | 16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis |
| title_full_unstemmed | 16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis |
| title_short | 16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis |
| title_sort | 16pdel lipid changes in ipsc derived neurons and function of fam57b in lipid metabolism and synaptogenesis |
| url | https://hdl.handle.net/1721.1/146841 |
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