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Sökning: id:"swepub:oai:DiVA.org:uu-509282" > Screening autism-as...

Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomics

Arora, Abishek (författare)
Karolinska Institute,Karolinska Institutet,Karolinska Inst, Ctr Neurodev Disorders KIND, Ctr Psychiat Res, Dept Womens & Childrens Hlth, BioClin J9:30,Visionsgatan 4, S-17156 Solna, Stockholm, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Region Stockhol, Sweden.,Karolinska University Hospital
Becker, Martin (författare)
Karolinska Institute,Karolinska University Hospital
Marques-Santos, Cátia M. (författare)
Uppsala University,Uppsala universitet,Institutionen för kemi - BMC
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Oksanen, Marika (författare)
Karolinska Institute,Karolinska University Hospital
Li, Danyang (författare)
Karolinska Institute,Karolinska University Hospital
Mastropasqua, Francesca (författare)
Karolinska Institute,Karolinska University Hospital
Watts, Michelle Evelyn (författare)
Karolinska Institute,Karolinska University Hospital
Arora, Manish (författare)
Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY USA.,Icahn School of Medicine at Mount Sinai
Falk, Anna (författare)
Karolinska Institute,Lund University,Lunds universitet,Neurala stamceller,Forskargrupper vid Lunds universitet,Neural stem cells,Lund University Research Groups
Daub, Carsten Oliver (författare)
Karolinska Institute,Karolinska Institutet,Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.;Sci Life Lab, Stockholm, Sweden.,Science for Life Laboratory (SciLifeLab)
Lanekoff, Ingela, Prof. 1975- (författare)
Uppsala University,Uppsala universitet,Institutionen för kemi - BMC
Tammimies, Kristiina (författare)
Karolinska Institute,Karolinska Institutet,Karolinska Inst, Ctr Neurodev Disorders KIND, Ctr Psychiat Res, Dept Womens & Childrens Hlth, BioClin J9:30,Visionsgatan 4, S-17156 Solna, Stockholm, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Region Stockhol, Sweden.,Karolinska University Hospital
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Karolinska Institutet Karolinska Inst, Ctr Neurodev Disorders KIND, Ctr Psychiat Res, Dept Womens & Childrens Hlth, BioClin J9:30,Visionsgatan 4, S-17156 Solna, Stockholm, Sweden;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Region Stockhol, Sweden. (creator_code:org_t)
Springer Nature, 2023
2023
Engelska.
Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

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