Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomics
Abstract Research continues to identify genetic variation, environmental exposures, and their mixtures underlying different diseases and conditions. There is a need for screening methods to understand the molecular outcomes of such factors. Here, we investigate a highly efficient and multiplexable,...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-37488-0 |
| _version_ | 1797789863806763008 |
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| author | Abishek Arora Martin Becker Cátia Marques Marika Oksanen Danyang Li Francesca Mastropasqua Michelle Evelyn Watts Manish Arora Anna Falk Carsten Oliver Daub Ingela Lanekoff Kristiina Tammimies |
| author_facet | Abishek Arora Martin Becker Cátia Marques Marika Oksanen Danyang Li Francesca Mastropasqua Michelle Evelyn Watts Manish Arora Anna Falk Carsten Oliver Daub Ingela Lanekoff Kristiina Tammimies |
| author_sort | Abishek Arora |
| collection | DOAJ |
| description | Abstract Research continues to identify genetic variation, environmental exposures, and their mixtures underlying different diseases and conditions. There is a need for screening methods to understand the molecular outcomes of such factors. Here, we investigate a highly efficient and multiplexable, fractional factorial experimental design (FFED) to study six environmental factors (lead, valproic acid, bisphenol A, ethanol, fluoxetine hydrochloride and zinc deficiency) and four human induced pluripotent stem cell line derived differentiating human neural progenitors. We showcase the FFED coupled with RNA-sequencing to identify the effects of low-grade exposures to these environmental factors and analyse the results in the context of autism spectrum disorder (ASD). We performed this after 5-day exposures on differentiating human neural progenitors accompanied by a layered analytical approach and detected several convergent and divergent, gene and pathway level responses. We revealed significant upregulation of pathways related to synaptic function and lipid metabolism following lead and fluoxetine exposure, respectively. Moreover, fluoxetine exposure elevated several fatty acids when validated using mass spectrometry-based metabolomics. Our study demonstrates that the FFED can be used for multiplexed transcriptomic analyses to detect relevant pathway-level changes in human neural development caused by low-grade environmental risk factors. Future studies will require multiple cell lines with different genetic backgrounds for characterising the effects of environmental exposures in ASD. |
| first_indexed | 2024-03-13T01:56:36Z |
| format | Article |
| id | doaj.art-a14618709be04c57acc85e78db8c8340 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-13T01:56:36Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-a14618709be04c57acc85e78db8c83402023-07-02T11:13:20ZengNature PortfolioScientific Reports2045-23222023-06-0113111510.1038/s41598-023-37488-0Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomicsAbishek Arora0Martin Becker1Cátia Marques2Marika Oksanen3Danyang Li4Francesca Mastropasqua5Michelle Evelyn Watts6Manish Arora7Anna Falk8Carsten Oliver Daub9Ingela Lanekoff10Kristiina Tammimies11Center of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Department of Women’s and Children’s Health, Karolinska InstitutetCenter of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Department of Women’s and Children’s Health, Karolinska InstitutetDepartment of Chemistry - BMC, Uppsala UniversityCenter of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Department of Women’s and Children’s Health, Karolinska InstitutetCenter of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Department of Women’s and Children’s Health, Karolinska InstitutetCenter of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Department of Women’s and Children’s Health, Karolinska InstitutetCenter of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Department of Women’s and Children’s Health, Karolinska InstitutetDepartment of Environmental Medicine and Public Health, Icahn School of Medicine at Mount SinaiDepartment of Neuroscience, Karolinska InstitutetDepartment of Biosciences and Nutrition, Karolinska InstitutetDepartment of Chemistry - BMC, Uppsala UniversityCenter of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Department of Women’s and Children’s Health, Karolinska InstitutetAbstract Research continues to identify genetic variation, environmental exposures, and their mixtures underlying different diseases and conditions. There is a need for screening methods to understand the molecular outcomes of such factors. Here, we investigate a highly efficient and multiplexable, fractional factorial experimental design (FFED) to study six environmental factors (lead, valproic acid, bisphenol A, ethanol, fluoxetine hydrochloride and zinc deficiency) and four human induced pluripotent stem cell line derived differentiating human neural progenitors. We showcase the FFED coupled with RNA-sequencing to identify the effects of low-grade exposures to these environmental factors and analyse the results in the context of autism spectrum disorder (ASD). We performed this after 5-day exposures on differentiating human neural progenitors accompanied by a layered analytical approach and detected several convergent and divergent, gene and pathway level responses. We revealed significant upregulation of pathways related to synaptic function and lipid metabolism following lead and fluoxetine exposure, respectively. Moreover, fluoxetine exposure elevated several fatty acids when validated using mass spectrometry-based metabolomics. Our study demonstrates that the FFED can be used for multiplexed transcriptomic analyses to detect relevant pathway-level changes in human neural development caused by low-grade environmental risk factors. Future studies will require multiple cell lines with different genetic backgrounds for characterising the effects of environmental exposures in ASD.https://doi.org/10.1038/s41598-023-37488-0 |
| spellingShingle | Abishek Arora Martin Becker Cátia Marques Marika Oksanen Danyang Li Francesca Mastropasqua Michelle Evelyn Watts Manish Arora Anna Falk Carsten Oliver Daub Ingela Lanekoff Kristiina Tammimies Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomics Scientific Reports |
| title | Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomics |
| title_full | Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomics |
| title_fullStr | Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomics |
| title_full_unstemmed | Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomics |
| title_short | Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomics |
| title_sort | screening autism associated environmental factors in differentiating human neural progenitors with fractional factorial design based transcriptomics |
| url | https://doi.org/10.1038/s41598-023-37488-0 |
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