Developing a cellular and genetic resource for studying genetic effects on biology. Large scale genetic studies have identified hundreds of alleles that are associated with risk of disease, including neurodevelopmental and psychiatric disorders, but mechanisms remain elusive. To study the functional effects of gene variants, we need access to human genetic backgrounds and relevant cell types. Human pluripotent stem cells (hPSCs) provide unprecedented access to the human tissues affected in disease, and new differentiation protocols give us the ability to generate purified and defined disease-relevant cell types. Through a large collaborative effort, we have established the Stanley Center Stem Cell Resource, a human cellular and genetic resource of hPSCs. We have assembled and annotated lines from hundreds of donors across a range of diagnoses and ancestral backgrounds. All cell lines undergo SNP analysis and whole genome sequencing to characterize genetic variation and enable downstream analyses.
High-dimensional phenotyping to define the genetic basis of cellular morphology.
Tegtmeyer M#, Arora J#, Asgari S#, Cimini B, Peirent E, Liyanage D, Way G, Weisbart E, Nathan A, Amariuta T, Eggan K, Haghighi M, McCarroll SA, Carpenter AE, Singh S*, Nehme R*, Raychaudhuri S*. bioRxiv 2023 and under review.
Pietilainen O, Trehan, A, Valakh V, Tegtmeyer M, Mitchell J, Meyer D, Gebre H, Chen T, Farhi SL, Eggan K, McCarroll SA, Nehme R. Cell Rep. 2023. PMID: 36640364.
Robust induction of functional astrocytes using NGN2 expression in human pluripotent stem cells.
Berryer MH#, Tegtmeyer M#, Binan L, Valakh V, Nathanson A, Trendafilova D, Crouse E, Klein J, Meyer D, Pietiläinen O, Rapino F, Farhi SL, Rubin LL, McCarroll SA, Nehme R*, Barrett LE*. iScience. 2023.
Greater ancestral diversity is needed in human pluripotent stem cell models.
Ghosh S*, Nehme R*, Barrett L*. Nat Commun. 2022. PMID: 36435871; PMCID: PMC9701202.
Tegtmeyer M and Nehme R. J Mol Biol. 2021. Aug 30;167221. PMID: 34474087
The 22q11.2 region regulates presynaptic gene-products linked to schizophrenia.
Nehme R#*, Pietilainen, O#*, Artomov, M, Tegtmeyer, M, Bell, C, Ganna, A, Singh, T, Trehan, A, Valakh V, Sherwood, J, Manning, D, Peirent, E, Malik, R, Guss, E, Hawes, D, Beccard, A, Bara, M, Hazelbaker, D, Zuccaro, E, Genovese, G, Loboda, AA, Neumann, A, Lilliehook, C, Kuismin, O, Hamalainen, E, Kurki, M, Hultman, C, Kahler, Paulo JA, Madison, J, Cohen, B, McPhie, D, Adolfsson, R, Perlis, R, Dolmestch, R, Farhi S, McCarroll S, Hyman S, Neale B, Barrett LE, Harper W, Palotie A, Daly M, Eggan K. Nat Commun. 2022. Jun 27;13(1):3690. PMID: 35760976. PMC9237031.
Using human pluripotent stem cell models to study autism in the era of big data.
Nehme R and Barrett LE. Mol Autism. 2020.11(1):21. PMID32293529.PMC7087382.
Mapping genetic effects on cellular phenotypes with “cell villages”.
Mitchell JM, Nemesh J, Ghosh S, Handsaker RE, Mello CJ, Meyer D, Raghunathan K, de Rivera M, Tegtmeyer M, Hawes D, Neumann A, Nehme R, Eggan K, McCarroll SA. bioRxiv and in revision.
Limone F, Mitchell JM, Guerra San Juan I, Smith JLM, Raghunathan K, Couto A, Ghosh SA, Meyer D, Mello CJ, Nemesh J, Smith BM, McCarroll S, Pietiläinen O, Nehme R, Eggan K. Cell Rep. 2022 Dec 23;111896. PMID: 36596304
Fan LZ, Nehme R, Adam Y, Jeung ES, Wu H, Arnold DB, Eggan K, Cohen A. Nat Methods. 2018. 15(10):823-831. PMID30275587.PMC6204345
Nehme R#, Zuccaro E#, Ghosh SD, Li C, Sherwood JL, Pietilainen O, Barrett LE, Limone F, Worringer KA, Kommineni S, Zang Y, Cacchiarelli D, Meissner A, Adolfsson R, Haggarty S, Madison J, Muller M, Arlotta P, Fu Z, Feng G and Eggan K. Cell Rep. 2018. 23(8):2509-2523. PMID29791859.PMC6003669.
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