Transcriptional landscape of the prenatal human brain

Miller, Jeremy A.; Ding, Song‐Lin; Sunkin, Susan M.; Smith, Kimberly A.; Ng, Lydia; Szafer, Aaron; Ebbert, Amanda; Riley, Zackery L.; Royall, Joshua J.; Aiona, Kaylynn; Arnold, James M.; Bennet, Crissa; Bertagnolli, Darren; Brouner, Krissy; Butler, Stephanie; Caldejon, Shiella; Carey, Anita; Cuhaciyan, Christine; Dalley, Rachel; Dee, Nick; Dolbeare, Tim; Facer, Benjamin A.C.; Feng, David; Fliss, Tim P.; Gee, Garrett; Goldy, Jeff; Gourley, Lindsey; Gregor, Benjamin W.; Gu, Guangyu; Howard, Robert; Jochim, Jayson M.; Kuan, Chihchau; Lau, Christopher; Lee, Chang Kyu; Lee, Felix; Lemon, Tracy; Lesnar, Phil; McMurray, Bergen; Mastan, Naveed; Mosqueda, Nerick; Naluai-Cecchini, Theresa; Ngo, N. Kiet; Nyhus, Julie; Oldre, Aaron; Olson, Eric C.; Parente, Jody; Parker, Patrick D.; Parry, Sheana; Stevens, Allison; Pletikos, Mihovil; Reding, Melissa; Roll, Kate; Sandman, David; Sarreal, Melaine; Shapouri, Sheila; Shapovalova, Nadiya V.; Shen, Elaine; Sjoquist, Nathan; Slaughterbeck, Clifford R.; Smith, Michael W.; Sodt, Andy J.; Williams, Derric; Zöllei, Lilla; Fischl, Bruce; Gerstein, Mark; Geschwind, Daniel H.; Glass, Ian A.; Hawrylycz, Michael; Hevner, Robert F.; Huang, Hao; Jones, Allan R.; Knowles, James A.; Levitt, Pat; Phillips, John W.; Šestan, Nenad; Wohnoutka, Paul; Dang, Chinh; Bernard, Amy; Hohmann, John G.; Lein, Ed

doi:10.1038/nature13185

Cited by 1,180 publications

(1,320 citation statements)

References 62 publications

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“…However, more recent studies in ferret (Reillo and Borrell, 2012) and macaque (Betizeau et al, 2013) have shown that the cellular composition of ISVZ and OSVZ is very similar and both contain oRG and IPCs than was previously appreciated. This is also in agreement with the finding that gene expression profiles of ISVZ and OSVZ in the human developing neocortex are closely related to each other (Fietz et al, 2012; Miller et al, 2014). …”

Section: Does the Isocortex Of All Eutherian Mammals Develop From A Gsupporting

confidence: 91%

From sauropsids to mammals and back: New approaches to comparative cortical development

Montiel

Vasistha

García-Moreno

et al. 2015

J of Comparative Neurology

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Evolution of the mammalian neocortex (isocortex) has been a persisting problem in neurobiology. While recent studies have attempted to understand the evolutionary expansion of the human neocortex from rodents, similar approaches have been used to study the changes between reptiles, birds, and mammals. We review here findings from the past decades on the development, organization, and gene expression patterns in various extant species. This review aims to compare cortical cell numbers and neuronal cell types to the elaboration of progenitor populations and their proliferation in these species. Several progenitors, such as the ventricular radial glia, the subventricular intermediate progenitors, and the subventricular (outer) radial glia, have been identified but the contribution of each to cortical layers and cell types through specific lineages, their possible roles in determining brain size or cortical folding, are not yet understood. Across species, larger, more diverse progenitors relate to cortical size and cell diversity. The challenge is to relate the radial and tangential expansion of the neocortex to the changes in the proliferative compartments during mammalian evolution and with the changes in gene expression and lineages evident in various sectors of the developing brain. We also review the use of recent lineage tracing and transcriptomic approaches to revisit theories and to provide novel understanding of molecular processes involved in specification of cortical regions. J. Comp. Neurol. 524:630–645, 2016. © 2015 The Authors. The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

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Section: Does the Isocortex Of All Eutherian Mammals Develop From A Gsupporting

confidence: 91%

From sauropsids to mammals and back: New approaches to comparative cortical development

Montiel

Vasistha

García-Moreno

et al. 2015

J of Comparative Neurology

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“…We narrowed down the candidate-gene list by excluding NHSL2 (Gene ID: 340527), AMER1 (Gene ID: 139285), PHKA1 (Gene ID: 5255) and RGAG1 (Gene ID: 57529) based on evolutionary analysis, gene expression profiles in tissues and protein topology position (Supplementary Figure 1). NHSL2 gene was excluded because there are no reports on association of rare variants in the NHSL2 gene, including the rs72630038 (SCV000221324) (MAF = 0.045 in 1000 Genomes Project Consortium 15 ) found in the Buryat patient, with any disorder; low expression of the gene in the cerebellum at prenatal period; 16,17 and that at least one mammalian species (hedgehog) bears the same rare amino-acid variant in NHSL2. Mutations in the AMER1 gene are known as genetic factors underlying osteopathia striata, cranial sclerosis and intellectual disability syndrome (OMIM: 300647 and 300373).…”

Section: Whole-genome Sequencingmentioning

confidence: 99%

Whole-genome sequencing identifies a novel ABCB7 gene mutation for X-linked congenital cerebellar ataxia in a large family of Mongolian ancestry

et al. 2015

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X-linked congenital cerebellar ataxia is a heterogeneous nonprogressive neurodevelopmental disorder with onset in early childhood. We searched for a genetic cause of this condition, previously reported in a Buryat pedigree of Mongolian ancestry from southeastern Russia. Using whole-genome sequencing on Illumina HiSeq 2000 platform, we found a missense mutation in the ABCB7 (ABC-binding cassette transporter B7) gene, encoding a mitochondrial transporter, involved in heme synthesis and previously associated with sideroblastic anemia and ataxia. The mutation resulting in a substitution of a highly conserved glycine to serine in position 682 is apparently a major causative factor of the cerebellar hypoplasia/atrophy found in affected individuals of a Buryat family who had no evidence of sideroblastic anemia. Moreover, in these affected men we also found the genetic defects in two other genes closely linked to ABCB7 on chromosome X: a deletion of a genomic region harboring the second exon of copper-transporter gene (ATP7A) and a complete deletion of PGAM4 (phosphoglycerate mutase family member 4) retrogene located in the intronic region of the ATP7A gene. Despite the deletion, eliminating the first of six metal-binding domains in ATP7A, no signs for Menkes disease or occipital horn syndrome associated with ATP7A mutations were found in male carriers. The role of the PGAM4 gene has been previously implicated in human reproduction, but our data indicate that its complete loss does not disrupt male fertility. Our finding links cerebellar pathology to the genetic defect in ABCB7 and ATP7A structural variant inherited as X-linked trait, and further reveals the genetic heterogeneity of X-linked cerebellar disorders.

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“…Given the many ways in which complex diseases arise, and for human brain diseases, the well‐recognized cellular heterogeneity of the brain, pinpointing cell types of interest, is important to further understand pathogenicity. Efforts to obtain brain samples (the most obviously relevant tissue for neurodegenerative diseases) for eQTL analyses are ongoing 8, 9, 10, 11, 12, 13. There has been a recent proliferation in the availability of cell‐type and tissue‐specific annotations, including brain tissue, for example, through the Roadmap Epigenomics Project14 and the PsychEncode Project 11.…”

Section: Introductionmentioning

confidence: 99%

Genomics implicates adaptive and innate immunity in Alzheimer's and Parkinson's diseases

Gagliano

Pouget

Hardy

et al. 2016

Ann Clin Transl Neurol

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ObjectivesWe assessed the current genetic evidence for the involvement of various cell types and tissue types in the etiology of neurodegenerative diseases, especially in relation to the neuroinflammatory hypothesis of neurodegenerative diseases.MethodsWe obtained large‐scale genome‐wide association study (GWAS) summary statistics from Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). We used multiple sclerosis (MS), an autoimmune disease of the central nervous system, as a positive control. We applied stratified LD score regression to determine if functional marks for cell type and tissue activity, and gene‐set lists were enriched for genetic heritability. We compared our results to those from two gene‐set enrichment methods (Ingenuity Pathway Analysis and enrichr).ResultsThere were no significant heritability enrichments for annotations marking genes active within brain regions, but there were significant heritability enrichments for annotations marking genes active within cell types that form part of both the innate and adaptive immune systems. We found this for MS (as expected) and also for AD and PD. The strongest signals were from the adaptive immune system (e.g., T cells) for PD, and from both the adaptive (e.g., T cells) and innate (e.g., CD14: a marker for monocytes, and CD15: a marker for neutrophils) immune systems for AD. Annotations from the liver were also significant for AD. Pathway analysis provided complementary results.InterpretationFor AD and PD, we found significant enrichment of heritability in annotations marking gene activity in immune cells.

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Transcriptional landscape of the prenatal human brain

Cited by 1,180 publications

References 62 publications

From sauropsids to mammals and back: New approaches to comparative cortical development

From sauropsids to mammals and back: New approaches to comparative cortical development

Whole-genome sequencing identifies a novel ABCB7 gene mutation for X-linked congenital cerebellar ataxia in a large family of Mongolian ancestry

Genomics implicates adaptive and innate immunity in Alzheimer's and Parkinson's diseases

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