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Using human pluripotent stem cell models to study autism in the era of big data / Ralda NEHME in Molecular Autism, 11 (2020)
[article]
Titre : Using human pluripotent stem cell models to study autism in the era of big data Type de document : Texte imprimé et/ou numérique Auteurs : Ralda NEHME, Auteur ; Lindy E. BARRETT, Auteur Article en page(s) : 21 p. Langues : Anglais (eng) Mots-clés : Differentiation esc Human brain In vivo Regulatory policy Sample size Variance hPSC iPSC Index. décimale : PER Périodiques Résumé : Advances in human pluripotent stem cell (hPSC) biology coupled with protocols to generate diverse brain cell types in vitro have provided neuroscientists with opportunities to dissect basic and disease mechanisms in increasingly relevant cellular substrates. At the same time, large data collections and analyses have facilitated unprecedented insights into autism genetics, normal human genetic variation, and the molecular landscape of the developing human brain. While such insights have enabled the investigation of key mechanistic questions in autism, they also highlight important limitations associated with the use of existing hPSC models. In this review, we discuss four such issues which influence the efficacy of hPSC models for studying autism, including (i) sources of variance, (ii) scale and format of study design, (iii) divergence from the human brain in vivo, and (iv) regulatory policies and compliance governing the use of hPSCs. Moreover, we advocate for a set of immediate and long-term priorities to address these issues and to accelerate the generation and reproducibility of data in order to facilitate future fundamental as well as therapeutic discoveries. En ligne : http://dx.doi.org/10.1186/s13229-020-00322-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427
in Molecular Autism > 11 (2020) . - 21 p.[article] Using human pluripotent stem cell models to study autism in the era of big data [Texte imprimé et/ou numérique] / Ralda NEHME, Auteur ; Lindy E. BARRETT, Auteur . - 21 p.
Langues : Anglais (eng)
in Molecular Autism > 11 (2020) . - 21 p.
Mots-clés : Differentiation esc Human brain In vivo Regulatory policy Sample size Variance hPSC iPSC Index. décimale : PER Périodiques Résumé : Advances in human pluripotent stem cell (hPSC) biology coupled with protocols to generate diverse brain cell types in vitro have provided neuroscientists with opportunities to dissect basic and disease mechanisms in increasingly relevant cellular substrates. At the same time, large data collections and analyses have facilitated unprecedented insights into autism genetics, normal human genetic variation, and the molecular landscape of the developing human brain. While such insights have enabled the investigation of key mechanistic questions in autism, they also highlight important limitations associated with the use of existing hPSC models. In this review, we discuss four such issues which influence the efficacy of hPSC models for studying autism, including (i) sources of variance, (ii) scale and format of study design, (iii) divergence from the human brain in vivo, and (iv) regulatory policies and compliance governing the use of hPSCs. Moreover, we advocate for a set of immediate and long-term priorities to address these issues and to accelerate the generation and reproducibility of data in order to facilitate future fundamental as well as therapeutic discoveries. En ligne : http://dx.doi.org/10.1186/s13229-020-00322-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427 Longitudinal Volumetric Brain Changes in Autism Spectrum Disorder Ages 6–35 Years / Nicholas LANGE in Autism Research, 8-1 (February 2015)
[article]
Titre : Longitudinal Volumetric Brain Changes in Autism Spectrum Disorder Ages 6–35 Years Type de document : Texte imprimé et/ou numérique Auteurs : Nicholas LANGE, Auteur ; Brittany G. TRAVERS, Auteur ; Erin D. BIGLER, Auteur ; Molly B. D. PRIGGE, Auteur ; Alyson L. FROEHLICH, Auteur ; Jared A. NIELSEN, Auteur ; Annahir N. CARIELLO, Auteur ; Brandon A. ZIELINSKI, Auteur ; Jeffrey S. ANDERSON, Auteur ; P. Thomas FLETCHER, Auteur ; Andrew A. ALEXANDER, Auteur ; Janet E. LAINHART, Auteur Article en page(s) : p.82-93 Langues : Anglais (eng) Mots-clés : adolescents adults children growth curve mixed effects MRI variance Index. décimale : PER Périodiques Résumé : Since the impairments associated with autism spectrum disorder (ASD) tend to persist or worsen from childhood into adulthood, it is of critical importance to examine how the brain develops over this growth epoch. We report initial findings on whole and regional longitudinal brain development in 100 male participants with ASD (226 high-quality magnetic resonance imaging [MRI] scans; mean inter-scan interval 2.7 years) compared to 56 typically developing controls (TDCs) (117 high-quality scans; mean inter-scan interval 2.6 years) from childhood into adulthood, for a total of 156 participants scanned over an 8-year period. This initial analysis includes between one and three high-quality scans per participant that have been processed and segmented to date, with 21% having one scan, 27% with two scans, and 52% with three scans in the ASD sample; corresponding percentages for the TDC sample are 30%, 30%, and 40%. The proportion of participants with multiple scans (79% of ASDs and 68% of TDCs) was high in comparison to that of large longitudinal neuroimaging studies of typical development. We provide volumetric growth curves for the entire brain, total gray matter (GM), frontal GM, temporal GM, parietal GM, occipital GM, total cortical white matter (WM), corpus callosum, caudate, thalamus, total cerebellum, and total ventricles. Mean volume of cortical WM was reduced significantly. Mean ventricular volume was increased in the ASD sample relative to the TDCs across the broad age range studied. Decreases in regional mean volumes in the ASD sample most often were due to decreases during late adolescence and adulthood. The growth curve of whole brain volume over time showed increased volumes in young children with autism, and subsequently decreased during adolescence to meet the TDC curve between 10 and 15 years of age. The volume of many structures continued to decline atypically into adulthood in the ASD sample. The data suggest that ASD is a dynamic disorder with complex changes in whole and regional brain volumes that change over time from childhood into adulthood. Autism Res 2015, 8: 82–93. En ligne : http://dx.doi.org/10.1002/aur.1427 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=256
in Autism Research > 8-1 (February 2015) . - p.82-93[article] Longitudinal Volumetric Brain Changes in Autism Spectrum Disorder Ages 6–35 Years [Texte imprimé et/ou numérique] / Nicholas LANGE, Auteur ; Brittany G. TRAVERS, Auteur ; Erin D. BIGLER, Auteur ; Molly B. D. PRIGGE, Auteur ; Alyson L. FROEHLICH, Auteur ; Jared A. NIELSEN, Auteur ; Annahir N. CARIELLO, Auteur ; Brandon A. ZIELINSKI, Auteur ; Jeffrey S. ANDERSON, Auteur ; P. Thomas FLETCHER, Auteur ; Andrew A. ALEXANDER, Auteur ; Janet E. LAINHART, Auteur . - p.82-93.
Langues : Anglais (eng)
in Autism Research > 8-1 (February 2015) . - p.82-93
Mots-clés : adolescents adults children growth curve mixed effects MRI variance Index. décimale : PER Périodiques Résumé : Since the impairments associated with autism spectrum disorder (ASD) tend to persist or worsen from childhood into adulthood, it is of critical importance to examine how the brain develops over this growth epoch. We report initial findings on whole and regional longitudinal brain development in 100 male participants with ASD (226 high-quality magnetic resonance imaging [MRI] scans; mean inter-scan interval 2.7 years) compared to 56 typically developing controls (TDCs) (117 high-quality scans; mean inter-scan interval 2.6 years) from childhood into adulthood, for a total of 156 participants scanned over an 8-year period. This initial analysis includes between one and three high-quality scans per participant that have been processed and segmented to date, with 21% having one scan, 27% with two scans, and 52% with three scans in the ASD sample; corresponding percentages for the TDC sample are 30%, 30%, and 40%. The proportion of participants with multiple scans (79% of ASDs and 68% of TDCs) was high in comparison to that of large longitudinal neuroimaging studies of typical development. We provide volumetric growth curves for the entire brain, total gray matter (GM), frontal GM, temporal GM, parietal GM, occipital GM, total cortical white matter (WM), corpus callosum, caudate, thalamus, total cerebellum, and total ventricles. Mean volume of cortical WM was reduced significantly. Mean ventricular volume was increased in the ASD sample relative to the TDCs across the broad age range studied. Decreases in regional mean volumes in the ASD sample most often were due to decreases during late adolescence and adulthood. The growth curve of whole brain volume over time showed increased volumes in young children with autism, and subsequently decreased during adolescence to meet the TDC curve between 10 and 15 years of age. The volume of many structures continued to decline atypically into adulthood in the ASD sample. The data suggest that ASD is a dynamic disorder with complex changes in whole and regional brain volumes that change over time from childhood into adulthood. Autism Res 2015, 8: 82–93. En ligne : http://dx.doi.org/10.1002/aur.1427 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=256