Abstract:
:Recent studies have established important roles of de novo mutations (DNMs) in autism spectrum disorders (ASDs). Here, we analyze DNMs in 262 ASD probands of Japanese origin and confirm the "de novo paradigm" of ASDs across ethnicities. Based on this consistency, we combine the lists of damaging DNMs in our and published ASD cohorts (total number of trios, 4,244) and perform integrative bioinformatics analyses. Besides replicating the findings of previous studies, our analyses highlight ATP-binding genes and fetal cerebellar/striatal circuits. Analysis of individual genes identified 61 genes enriched for damaging DNMs, including ten genes for which our dataset now contributes to statistical significance. Screening of compounds altering the expression of genes hit by damaging DNMs reveals a global downregulating effect of valproic acid, a known risk factor for ASDs, whereas cardiac glycosides upregulate these genes. Collectively, our integrative approach provides deeper biological and potential medical insights into ASDs.
journal_name
Cell Repjournal_title
Cell reportsauthors
Takata A,Miyake N,Tsurusaki Y,Fukai R,Miyatake S,Koshimizu E,Kushima I,Okada T,Morikawa M,Uno Y,Ishizuka K,Nakamura K,Tsujii M,Yoshikawa T,Toyota T,Okamoto N,Hiraki Y,Hashimoto R,Yasuda Y,Saitoh S,Ohashi K,Sakaidoi
10.1016/j.celrep.2017.12.074subject
Has Abstractpub_date
2018-01-16 00:00:00pages
734-747issue
3issn
2211-1247pii
S2211-1247(17)31911-3journal_volume
22pub_type
杂志文章相关文献
Cell Reports文献大全abstract::Dendritic cells (DCs) and macrophages (Mϕs) share close developmental pathways and functional features, leading to blurring of the boundaries between these two cell lineages. However, a deeper understanding of DC and Mϕ ontogeny and more refined phenotypic and functional characterizations have helped to delineate pre-...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.10.024
更新日期:2017-10-31 00:00:00
abstract::Placental development is a key event in mammalian reproduction and embryogenesis. However, the molecular basis underlying placental development is not fully understood. Here, we conduct a forward genetic screen to identify regulators for extraembryonic development and identify Zfp281 as a key factor. Zfp281 overexpres...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.04.028
更新日期:2019-05-07 00:00:00
abstract::The guardian of the genome, p53, is often mutated in cancer and may contribute to therapeutic resistance. Given that p53 is intact and functional in normal tissues, we harnessed its potential to inhibit the growth of p53-deficient cancer cells. Specific activation of p53 in normal fibroblasts selectively induced apopt...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.12.020
更新日期:2014-01-30 00:00:00
abstract::Organisms need to assess their nutritional state and adapt their digestive capacity to the demands for various nutrients. Modulation of digestive enzyme production represents a rational step to regulate nutriment uptake. However, the role of digestion in nutrient homeostasis has been largely neglected. In this study, ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.08.064
更新日期:2014-10-09 00:00:00
abstract::Ubiquitin is post-translationally modified by phosphorylation at several sites, but the consequences of these modifications are largely unknown. Here, we synthesize multi-milligram quantities of ubiquitin phosphorylated at serine 20, serine 57, and serine 65 via genetic code expansion. We use these phosphoubiquitins f...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.06.064
更新日期:2016-07-26 00:00:00
abstract::The small GTPase Arl13b is enriched in primary cilia and regulates Sonic hedgehog (Shh) signaling. During neural development, Shh controls patterning and proliferation through a canonical, transcription-dependent pathway that requires the primary cilium. Additionally, Shh controls axon guidance through a non-canonical...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.11.015
更新日期:2019-12-10 00:00:00
abstract::In mammalian skin, Merkel cells are mechanoreceptor cells that are required for the perception of gentle touch. Recent evidence indicates that mature Merkel cells descend from the proliferative layer of skin epidermis; however, the stem cell niche for Merkel cell homeostasis has not been reported. Here, we provide gen...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.04.026
更新日期:2013-06-27 00:00:00
abstract::Amphotericin, miconazole, and ciclopirox are antifungal agents from three different drug classes that can effectively kill planktonic yeast, yet their complete fungicidal mechanisms are not fully understood. Here, we employ a systems biology approach to identify a common oxidative-damage cellular death pathway trigger...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2012.12.021
更新日期:2013-02-21 00:00:00
abstract::RNA polymerase II transcripts receive a protective 5',5'-triphosphate-linked 7-methylguanosine (m7G) cap, and its removal by decapping enzymes like DCP2 is critical for initiation of RNA decay. Alternative RNA caps can be acquired when transcription initiation uses metabolites like nicotinamide adenine dinucleotide (N...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.11.108
更新日期:2019-12-24 00:00:00
abstract::Alcohol produces both stimulant and sedative effects in humans and rodents. In humans, alcohol abuse disorder is associated with a higher stimulant and lower sedative responses to alcohol. Here, we show that this association is conserved in mice and demonstrate a causal link with another liability factor: low expressi...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.09.059
更新日期:2019-10-29 00:00:00
abstract::Glioblastoma multiforme (GBM) is among the most aggressive of human cancers. Although differentiation therapy has been proposed as a potential approach to treat GBM, the mechanisms of induced differentiation remain poorly defined. Here, we established an induced differentiation model of GBM using cAMP activators that ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.12.037
更新日期:2017-01-10 00:00:00
abstract::Mechanistic (or mammalian) target of rapamycin complex 1 (mTORC1) integrates signals from growth factors and nutrients to control biosynthetic processes, including protein, lipid, and nucleic acid synthesis. We find that the mTORC1 pathway is responsive to changes in purine nucleotides in a manner analogous to its sen...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.10.029
更新日期:2017-10-31 00:00:00
abstract::Ring NTPases are a class of ubiquitous molecular motors involved in basic biological partitioning processes. dsDNA viruses encode ring ATPases that translocate their genomes to near-crystalline densities within pre-assembled viral capsids. Here, X-ray crystallography, cryoEM, and biochemical analyses of the dsDNA pack...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.01.058
更新日期:2016-03-01 00:00:00
abstract::Ependymomas exist within distinct genetic subgroups, but the molecular diversity within individual ependymomas is unknown. We perform multiplatform molecular profiling of 6 spatially distinct samples from an ependymoma with C11orf95-RELA fusion. DNA methylation and RNA sequencing distinguish clusters of samples accord...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.01.018
更新日期:2020-02-04 00:00:00
abstract::The first cell fate choice of the preimplantation embryo generates the extraembryonic trophoblast and embryonic epiblast lineages. Embryonic stem cells (ESCs) and trophoblast stem cells (TSCs) can be utilized to investigate molecular mechanisms of this first cell fate decision. It has been established that ESCs can be...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.04.040
更新日期:2017-05-09 00:00:00
abstract::Complex architectural rearrangements are associated to the control of the HoxD genes in different cell types; yet, how they are implemented in single cells remains unknown. By use of polymer models, we dissect the locus 3D structure at the single DNA molecule level in mouse embryonic stem and cortical neuronal cells, ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.07.013
更新日期:2019-08-06 00:00:00
abstract::Training-dependent increases in c-fos have been used to identify engram cells encoding long-term memories (LTMs). However, the interaction between transcription factors required for LTM, including CREB and c-Fos, and activating kinases such as phosphorylated ERK (pERK) in the establishment of memory engrams has been u...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.11.022
更新日期:2018-12-04 00:00:00
abstract::The efficient generation of hematopoietic stem cells from human pluripotent stem cells is dependent on the appropriate specification of the definitive hematopoietic program during differentiation. In this study, we used T lymphocyte potential to track the onset of definitive hematopoiesis from human embryonic and indu...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2012.11.003
更新日期:2012-12-27 00:00:00
abstract::Adrenergic receptors are highly homologous while at the same time display a wide diversity of ligand and G-protein binding, and understanding this diversity is key for designing selective or biased drugs for them. Here, we determine two crystal structures of the α2A adrenergic receptor (α2AAR) in complex with a partia...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.10.088
更新日期:2019-12-03 00:00:00
abstract::The Piwi-piRNA pathway is well known for its germline function, yet its somatic role remains elusive. We show here that Piwi is required autonomously not only for germline stem cell (GSC) but also for somatic cyst stem cell (CySC) maintenance in the Drosophila testis. Reducing Piwi activity in the testis caused defect...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.06.004
更新日期:2015-07-07 00:00:00
abstract::The heavy chain IGHV1-69 germline gene exhibits a high level of polymorphism and shows biased use in protective antibody (Ab) responses to infections and vaccines. It is also highly expressed in several B cell malignancies and autoimmune diseases. G6 is an anti-idiotypic monoclonal Ab that selectively binds to IGHV1-6...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.11.056
更新日期:2017-12-12 00:00:00
abstract::FAM46C is a non-canonical poly(A) polymerase uniquely mutated in up to 20% of multiple myeloma (MM) patients, implying a tissue-specific tumor suppressor function. Here, we report that FAM46C selectively stabilizes mRNAs encoding endoplasmic reticulum (ER)-targeted proteins, thereby concertedly enhancing the expressio...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.108162
更新日期:2020-09-22 00:00:00
abstract::DNA methylation provides a mechanism by which environmental factors can control insulin sensitivity in obesity. Here, we assessed DNA methylation in skeletal muscle from obese people before and after Roux-en-Y gastric bypass (RYGB). Obesity was associated with altered expression of a subset of genes enriched in metabo...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.03.018
更新日期:2013-04-25 00:00:00
abstract::Glucagon-like peptide-1 receptor (GLP-1R) agonists used to treat type 2 diabetes mellitus often produce nausea, vomiting, and in some patients, undesired anorexia. Notably, these behavioral effects are caused by direct central GLP-1R activation. Herein, we describe the creation of a GLP-1R agonist conjugate with modif...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.107768
更新日期:2020-06-16 00:00:00
abstract::Activation of the transcription factor NF-κB is essential for innate immune function and requires strict regulation. The micronutrient zinc modulates proper host defense, and zinc deficiency is associated with elevated inflammation and worse outcomes in response to bacterial infection and sepsis. Previous studies sugg...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.01.009
更新日期:2013-02-21 00:00:00
abstract::A mature olfactory sensory neuron (OSN) of the main olfactory epithelium (MOE) typically expresses one allele of one odorant receptor (OR) gene. It is widely thought that the great majority of the 1,141 intact mouse OR genes are expressed in one of four MOE zones (or bands or stripes), which are largely non-overlappin...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.02.110
更新日期:2020-03-24 00:00:00
abstract::Viral vectors enable foreign proteins to be expressed in brains of non-genetic species, including non-human primates. However, viruses targeting specific neuron classes have proved elusive. Here we describe viral promoters and strategies for accessing GABAergic interneurons and their molecularly defined subsets in the...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.02.011
更新日期:2019-03-05 00:00:00
abstract::Both strands of human mtDNA are transcribed in continuous, multigenic units that are cleaved into the mature rRNAs, tRNAs, and mRNAs required for respiratory chain biogenesis. We sought to systematically identify nuclear-encoded proteins that contribute to processing of mtRNAs within the organelle. First, we devised a...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.03.035
更新日期:2014-05-08 00:00:00
abstract::BRCA1 is a tumor suppressor found to be mutated in hereditary breast and ovarian cancer and plays key roles in the maintenance of genomic stability by homologous recombination repair. It is recruited to damaged chromatin as a component of the BRCA1-A deubiquitinase, which cleaves K63-linked ubiquitin chains attached t...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.11.063
更新日期:2016-12-20 00:00:00
abstract::Modulating chromatin through histone methylation orchestrates numerous cellular processes. SETD2-dependent trimethylation of histone H3K36 is associated with active transcription. Here, we define a role for H3K36 trimethylation in homologous recombination (HR) repair in human cells. We find that depleting SETD2 genera...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.05.026
更新日期:2014-06-26 00:00:00