Transcriptomics

  • Article
    | Open Access

    The molecular mechanism by which clock neurons transmit timing information to non-clock neurons is poorly understood. Here, the authors show that circadian clocks drive rhythmic expression of hundreds of genes in mushroom body neurons and drive calcium rhythms via NF1-cAMP/PKAC1 signalling in Drosophila.

    • Pedro Machado Almeida
    • , Blanca Lago Solis
    •  & Emi Nagoshi
  • Article
    | Open Access

    As corals struggle to survive under climate change, it is crucial to know whether they can withstand increasing seawater temperatures. Using a controlled thermal stress experiment across three divergent coral holobionts, this study examines metatranscriptomic responses to heat stress corresponding to the coral host, photosymbionts and associated microbiota.

    • Viridiana Avila-Magaña
    • , Bishoy Kamel
    •  & Mónica Medina
  • Article
    | Open Access

    Single-cell profiling has led to the identification of diverse cell types. Here, the authors generate a harmonized cell atlas of the mouse post-natal spinal cord. They also provide spatial analysis of the distribution of the identified cell types and an open-source cell type classifier.

    • Daniel E. Russ
    • , Ryan B. Patterson Cross
    •  & Ariel J. Levine
  • Article
    | Open Access

    A comprehensive analysis of the ocular networks among various tissues is necessary to understand eye physiology in health and disease. Here the authors present a multi-species single-cell transcriptomic atlas consisting of cells of the cornea, iris, ciliary body, neural retina, retinal pigmented epithelium, and choroid.

    • Pradeep Gautam
    • , Kiyofumi Hamashima
    •  & Yuin-Han Loh
  • Article
    | Open Access

    Retinoblastoma is the most frequent intraocular paediatric malignancy whose molecular basis remains poorly understood. Here, the authors perform multi-omic analysis and identify two subtypes; one in a cone differentiated state and one more aggressive showing cone dedifferentiation and expressing neuronal markers.

    • Jing Liu
    • , Daniela Ottaviani
    •  & François Radvanyi
  • Article
    | Open Access

    Non-human primate models of autism spectrum disorder (ASD) are few and not well characterised. Here, the authors describe synaptic function and gene expression changes in a marmoset model of ASD from birth to juvenile, highlighting its similarity to features observed in human ASD.

    • Satoshi Watanabe
    • , Tohru Kurotani
    •  & Noritaka Ichinohe
  • Article
    | Open Access

    Alternative polyadenylation regulates localization, half-life and translation of mRNA isoforms. Here the authors investigate alternative polyadenylation using single cell RNA sequencing data from mouse embryos and identify 3’-UTR isoforms that are regulated across cell types and developmental time.

    • Vikram Agarwal
    • , Sereno Lopez-Darwin
    •  & Jay Shendure
  • Article
    | Open Access

    RNA polyadenosine tails are important for the export, translation and stability of mRNAs and play a role in non-coding RNA biogenesis. Here the authors measure yeast poly(A) tail lengths by direct RNA sequencing, revealing its dynamics in yeast exonuclease, deadenylase and poly(A) polymerase mutants.

    • Agnieszka Tudek
    • , Paweł S. Krawczyk
    •  & Andrzej Dziembowski
  • Article
    | Open Access

    Spatial analysis of RNAseq data is important. Here the authors report a method for transcriptome profiling combined with photo-isolation chemistry to allow determination of expression profiles specifically from photo-irradiated regions of interest which they use in mouse brains and embryonic tissues.

    • Mizuki Honda
    • , Shinya Oki
    •  & Yasuyuki Ohkawa
  • Article
    | Open Access

    Glucocorticoids (GC) are reported to block cancer cell proliferation, but the mode of action is unclear. Here the authors show that glucocorticoid receptor activation induces cancer cell dormancy in lung cancer by regulating CDKN1C expression through a distal enhancer, and these dormant cells are addicted to IGF-1R signalling pathway.

    • Stefan Prekovic
    • , Karianne Schuurman
    •  & Wilbert Zwart
  • Article
    | Open Access

    Single-cell RNA-seq reveals the cellular heterogeneity in development and disease. Here the authors present a single-nucleus RNA-seq2 that allows deep characterization of nuclei isolated from frozen archived tissues, apply it for transcriptional profiling of individual hepatocytes, and determine a functional crosstalk between liver zonation and ploidy.

    • M. L. Richter
    • , I. K. Deligiannis
    •  & C. P. Martinez-Jimenez
  • Article
    | Open Access

    Welwitschia mirabilis is a unique plant that only has two leaves, but it can survive in hostile conditions of the African desert. Here, the authors report its chromosome-level genome assembly and discuss how gene function and regulation have given rise to its unique morphology and environmental adaptions.

    • Tao Wan
    • , Zhiming Liu
    •  & Qingfeng Wang
  • Article
    | Open Access

    It remains unclear how spatial information controls endothelial cell identity and behavior in the developing heart. Here the authors perform single cell RNA sequencing at key developmental timepoints in mice to interrogate cellular contributions to coronary vessel patterning and maturation in the epicardium.

    • Pearl Quijada
    • , Michael A. Trembley
    •  & Eric M. Small
  • Article
    | Open Access

    Transcriptomic analysis may provide information about the differentiation state and cell of origin of a cancer. Here, the authors assess mRNA signals in 1300 childhood and adult renal tumors and report a fetal origin of childhood tumors and no dedifferentiation of adult tumors.

    • Matthew D. Young
    • , Thomas J. Mitchell
    •  & Sam Behjati
  • Article
    | Open Access

    Whether the adult testis harbours a somatic progenitor population is unknown. Here, the authors provide evidence that the testis interstitial cells expressing the transcription factor Tcf21 maintain adult testis homeostasis during aging, and act as potential reserve somatic progenitors following injury.

    • Yu-chi Shen
    • , Adrienne Niederriter Shami
    •  & Saher Sue Hammoud
  • Article
    | Open Access

    Single cell RNA-seq loses spatial information of gene expression in multicellular systems because tissue must be dissociated. Here, the authors show the spatial gene expression profiles can be both accurately and robustly reconstructed by a new computational method using a generative linear mapping, Perler.

    • Yasushi Okochi
    • , Shunta Sakaguchi
    •  & Honda Naoki
  • Article
    | Open Access

    Gliomas are tumors often associated with epigenetics-related gene deregulation. Here the authors reveal an atlas of active enhancers and promoters in benign and malignant gliomas by performing whole-genome mapping of chromatin accessibility, histone modifications, DNA methylation patterns and transcriptome analysis simultaneously in multiple tumor samples.

    • Karolina Stępniak
    • , Magdalena A. Machnicka
    •  & Bartek Wilczyński
  • Article
    | Open Access

    Early stages of embryogenesis are known to depend on subcellular localization and transport of maternal mRNA, but systematic analyses have been hindered by a lack of methods for tracking of RNA. Here the authors combine spatially-resolved transcriptomics and single-cell RNA labeling to perform a spatio-temporal analysis of the transcriptome during early zebrafish development, revealing insights into this process.

    • Karoline Holler
    • , Anika Neuschulz
    •  & Jan Philipp Junker
  • Article
    | Open Access

    The heterogeneity of tumor evolution from AR-positive, adenocarcinoma to AR-negative, neuroendocrine prostate cancer (NEPC) is not fully characterized. Here the authors generate a mouse model to show that Rb1 loss and MYCN overexpression accelerates the progression to AR-negative NEPC and identify emergence of distinct subpopulations of NEPC cells.

    • Nicholas J. Brady
    • , Alyssa M. Bagadion
    •  & David S. Rickman
  • Article
    | Open Access

    Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.

    • Mathys Grapotte
    • , Manu Saraswat
    •  & Charles-Henri Lecellier
  • Article
    | Open Access

    A feature of cohesin mutations in patients with Cornelia de Lange Syndrome (CdLS) is intellectual disability, but the underlying mechanisms have remained obscure. Here the authors show gene expression is deregulated in CdLS neurons and is recapitulated in a mouse model with cohesin depletion, which can be restored by re-expression of cohesin.

    • Felix D. Weiss
    • , Lesly Calderon
    •  & Matthias Merkenschlager
  • Article
    | Open Access

    Identifying enriched gene sets in transcriptomic data is routine analysis. Here, the authors show that conventional gene category enrichment analysis (GCEA) applied to brain-wide atlas data yields biased results and develop a flexible ensemble-based null model framework to enable appropriate inference in GCEA.

    • Ben D. Fulcher
    • , Aurina Arnatkeviciute
    •  & Alex Fornito
  • Article
    | Open Access

    After injury to the nervous system, many neurons fail to initiate transcriptional programs needed for axon growth. Here the authors examine co-operative binding of factors to regulatory DNA to predict combinations that improve axon growth when ectopically co-expressed.

    • Ishwariya Venkatesh
    • , Vatsal Mehra
    •  & Murray G. Blackmore
  • Article
    | Open Access

    The full heterogeneity and different functional roles of cholinergic neurons in the adult spinal cord remain to be defined. Here the authors develop a targeted single nuclear RNA sequencing approach and use it to identify an array of cholinergic interneurons, as well as visceral and skeletal motor neurons.

    • Mor R. Alkaslasi
    • , Zoe E. Piccus
    •  & Claire E. Le Pichon
  • Article
    | Open Access

    As human skeletal muscle ages, gene expression programs change and reflect damage accumulation and homeostatic resilience mechanisms. Here, the authors present a detailed framework of the global transcriptome that characterizes skeletal muscle during aging in healthy individuals.

    • Robert A. Tumasian III
    • , Abhinav Harish
    •  & Luigi Ferrucci
  • Article
    | Open Access

    Short read RNA sequencing and DNA sequence contain useful information for profiling polyadenylation sites, but each also possesses inherent limitations when examined independently. Aptardi combines these data and significantly improves annotation of polyadenylation sites in the expressed transcriptome.

    • Ryan Lusk
    • , Evan Stene
    •  & Laura M. Saba
  • Article
    | Open Access

    Image features from histological slides can be used as informative endophenotypes in association studies for tissue-localized pathologies. Here, the authors develop ImageCCA, a framework for joint analysis of paired gene expression and histology data derived from automatically extracted image features.

    • Jordan T. Ash
    • , Gregory Darnell
    •  & Barbara E. Engelhardt
  • Article
    | Open Access

    It is unclear how changes in gene expression are induced by changes in oxygen levels during late lung development. Here, the authors provide data from MULTI-seq scRNAseq in mice showing exposure to higher oxygen levels affects cell fates, especially for alveolarisation, and define gene/cell signatures of impaired lung development under hyperoxia.

    • Maria Hurskainen
    • , Ivana Mižíková
    •  & Bernard Thébaud
  • Article
    | Open Access

    Malignant rhabdoid tumours (MRT) have been suggested to originate in the ectoderm-derived neural crest. Here, the authors analyse MRTs using phylogenetics, scRNA-seq, and patient-derived organoids; they find evidence for an MRT origin in the neural crest lineage and suggest differentiation treatment with HDAC/mTOR inhibitors.

    • Lars Custers
    • , Eleonora Khabirova
    •  & Jarno Drost
  • Article
    | Open Access

    The response to hypoxia can significantly impact oncogenic processes. Here, the authors define the early transcriptional response to acute hypoxia and identify HIF1A target genes as part of this acute response, providing a resource for investigating context-dependent roles of HIF1A in the biology of cancer.

    • Zdenek Andrysik
    • , Heather Bender
    •  & Joaquin M. Espinosa
  • Article
    | Open Access

    Leukaemic stem cells drive acute myeloid leukaemia (AML) progression and relapse but they are incompletely characterized. Here, the authors combine single-cell transcriptomics and clonal tracking using nuclear and mitochondrial somatic variants to distinguish healthy, pre-leukaemic and leukaemic stem cells in AML.

    • Lars Velten
    • , Benjamin A. Story
    •  & Lars M. Steinmetz
  • Article
    | Open Access

    Understanding the molecular effects of disease variants in relevant tissues is essential to understanding and treating disease. Here, the authors discover expression and protein quantitative trait loci in cartilage and synovium from 115 osteoarthritis patients to pinpoint genes of action and potential drug treatments.

    • Julia Steinberg
    • , Lorraine Southam
    •  & Eleftheria Zeggini
  • Article
    | Open Access

    Carbon dots have attracted much attention for biomedical applications but potential degradation and associated toxicity are still poorly understood. Here, the authors report on a study into the photo-degradation of carbon dots, the products produced and associated cytotoxicity.

    • Yue-Yue Liu
    • , Nan-Yang Yu
    •  & Ai-Jun Miao
  • Article
    | Open Access

    Single cell genomics uses cells from the same individual, or pseudoreplicates, that can introduce biases and inflate type I error rates. Here the authors apply generalized linear mixed models with a random effect for individual, to properly account for both zero inflation and the correlation structure among cells within an individual.

    • Kip D. Zimmerman
    • , Mark A. Espeland
    •  & Carl D. Langefeld
  • Article
    | Open Access

    Genome-wide studies of de novo genes have tended to focus on genomic open reading frames (ORFs). Here, Blevins et al. use deep transcriptomics and synteny information to identify de novo transcripts in the yeast Saccharomyces cerevisiae, many of which are expressed from the alternative DNA strand.

    • William R. Blevins
    • , Jorge Ruiz-Orera
    •  & M. Mar Albà