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  1. Single-Cell Alternative Splicing Analysis with Expedition Reveals Splicing Dynamics during Neuron Differentiation.

    Molecular cell · 2017 · 67(1): 148-161.e5

    Alternative splicing (AS) generates isoform diversity for cellular identity and homeostasis in multicellular life. Although AS variation has been observed among single cells, little is known about the biological or evolutionary significance of such variation. We developed Expedition, a computational …

    PMID 28673540 DOI ↗

  2. Pseudotemporal Ordering of Single Cells Reveals Metabolic Control of Postnatal β Cell Proliferation.

    Cell metabolism · 2017 · 25(5): 1160-1175.e11

    Pancreatic β cell mass for appropriate blood glucose control is established during early postnatal life. β cell proliferative capacity declines postnatally, but the extrinsic cues and intracellular signals that cause this decline remain unknown. To obtain a high-resolution map of …

    PMID 28467932 DOI ↗

  3. Early transcriptional and epigenetic regulation of CD8<sup>+</sup> T cell differentiation revealed by single-cell RNA sequencing.

    Nature immunology · 2017 · 18(4): 422-432

    During microbial infection, responding CD8<sup>+</sup> T lymphocytes differentiate into heterogeneous subsets that together provide immediate and durable protection. To elucidate the dynamic transcriptional changes that underlie this process, we applied a single-cell RNA-sequencing approach and analyzed individual CD8<sup>+</sup> T lymphocytes …

    PMID 28218746 DOI ↗

  4. Interaction Landscape of Inherited Polymorphisms with Somatic Events in Cancer.

    Cancer discovery · 2017 · 7(4): 410-423

    Recent studies have characterized the extensive somatic alterations that arise during cancer. However, the somatic evolution of a tumor may be significantly affected by inherited polymorphisms carried in the germline. Here, we analyze genomic data for 5,954 tumors to reveal …

    PMID 28188128 DOI ↗

  5. CRISPR/Cas9-mediated integration enables TAG-eCLIP of endogenously tagged RNA binding proteins.

    Methods (San Diego, Calif.) · 2017 · 118-119: 50-59

    Identification of in vivo direct RNA targets for RNA binding proteins (RBPs) provides critical insight into their regulatory activities and mechanisms. Recently, we described a methodology for enhanced crosslinking and immunoprecipitation followed by high-throughput sequencing (eCLIP) using antibodies against endogenous …

    PMID 28003131 DOI ↗

  6. High-Throughput and Cost-Effective Characterization of Induced Pluripotent Stem Cells.

    Stem cell reports · 2017 · 8(4): 1101-1111

    Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) offers the possibility of studying the molecular mechanisms underlying human diseases in cell types difficult to extract from living patients, such as neurons and cardiomyocytes. To date, studies have been published …

    PMID 28410643 DOI ↗

  7. iPSCORE: A Resource of 222 iPSC Lines Enabling Functional Characterization of Genetic Variation across a Variety of Cell Types.

    Stem cell reports · 2017 · 8(4): 1086-1100

    Large-scale collections of induced pluripotent stem cells (iPSCs) could serve as powerful model systems for examining how genetic variation affects biology and disease. Here we describe the iPSCORE resource: a collection of systematically derived and characterized iPSC lines from 222 …

    PMID 28410642 DOI ↗

  8. Biallelic mutations in the 3' exonuclease TOE1 cause pontocerebellar hypoplasia and uncover a role in snRNA processing.

    Nature genetics · 2017 · 49(3): 457-464

    Deadenylases are best known for degrading the poly(A) tail during mRNA decay. The deadenylase family has expanded throughout evolution and, in mammals, consists of 12 Mg<sup>2+</sup>-dependent 3'-end RNases with substrate specificity that is mostly unknown. Pontocerebellar hypoplasia type 7 (PCH7) …

    PMID 28092684 DOI ↗

  9. Systematic review of dementia prevalence and incidence in United States race/ethnic populations.

    Alzheimer's & dementia : the journal of the Alzheimer's Association · 2017 · 13(1): 72-83

    To identify incidence and prevalence of dementia in racial and ethnic populations in the United States. A systematic review of literature. A total of 1215 studies were reviewed; 114 were included. Dementia prevalence rates reported for age 65+ years from …

    PMID 27599209 DOI ↗

  10. Tethered Function Assays as Tools to Elucidate the Molecular Roles of RNA-Binding Proteins.

    Advances in experimental medicine and biology · 2016 · 907: 61-88

    Dynamic regulation of RNA molecules is critical to the survival and development of cells. Messenger RNAs are transcribed in the nucleus as intron-containing pre-mRNAs and bound by RNA-binding proteins, which control their fate by regulating RNA stability, splicing, polyadenylation, translation, …

    PMID 27256382 DOI ↗

  11. Experimental and Computational Considerations in the Study of RNA-Binding Protein-RNA Interactions.

    Advances in experimental medicine and biology · 2016 · 907: 1-28

    After an RNA is transcribed, it undergoes a variety of processing steps that can change the encoded protein sequence (through alternative splicing and RNA editing), regulate the stability of the RNA, and control subcellular localization, timing, and rate of translation. …

    PMID 27256380 DOI ↗

  12. RNA-binding protein CPEB1 remodels host and viral RNA landscapes.

    Nature structural & molecular biology · 2016 · 23(12): 1101-1110

    Host and virus interactions occurring at the post-transcriptional level are critical for infection but remain poorly understood. Here, we performed comprehensive transcriptome-wide analyses revealing that human cytomegalovirus (HCMV) infection results in widespread alternative splicing (AS), shortening of 3' untranslated regions …

    PMID 27775709 DOI ↗

  13. MicroRNA-101 Regulates Multiple Developmental Programs to Constrain Excitation in Adult Neural Networks.

    Neuron · 2016 · 92(6): 1337-1351

    A critical feature of neural networks is that they balance excitation and inhibition to prevent pathological dysfunction. How this is achieved is largely unknown, although deficits in the balance contribute to many neurological disorders. We show here that a microRNA …

    PMID 27939580 DOI ↗

  14. Predicting the functional states of human iPSC-derived neurons with single-cell RNA-seq and electrophysiology.

    Molecular psychiatry · 2016 · 21(11): 1573-1588

    Human neural progenitors derived from pluripotent stem cells develop into electrophysiologically active neurons at heterogeneous rates, which can confound disease-relevant discoveries in neurology and psychiatry. By combining patch clamping, morphological and transcriptome analysis on single-human neurons in vitro, we defined …

    PMID 27698428 DOI ↗

  15. Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System.

    Neuron · 2016 · 92(4): 780-795

    HnRNPA2B1 encodes an RNA binding protein associated with neurodegeneration. However, its function in the nervous system is unclear. Transcriptome-wide crosslinking and immunoprecipitation in mouse spinal cord discover UAGG motifs enriched within ∼2,500 hnRNP A2/B1 binding sites and an unexpected role …

    PMID 27773581 DOI ↗

  16. The Calcineurin Variant CnAβ1 Controls Mouse Embryonic Stem Cell Differentiation by Directing mTORC2 Membrane Localization and Activation.

    Cell chemical biology · 2016 · 23(11): 1372-1382

    Embryonic stem cells (ESC) have the potential to generate all the cell lineages that form the body. However, the molecular mechanisms underlying ESC differentiation and especially the role of alternative splicing in this process remain poorly understood. Here, we show …

    PMID 27746127 DOI ↗

  17. Making the cut in the dark genome.

    Science (New York, N.Y.) · 2016 · 354(6313): 705-706

    PMID 27846591 DOI ↗

  18. From Protein-RNA Predictions toward a Peptide-RNA Code.

    Molecular cell · 2016 · 64(3): 437-438

    The RNA field is undergoing a renaissance, with a deluge of proteins being identified to bind RNA. Two reports now introduce proteome-wide approaches that identify the peptides that are crosslinked to RNA (Castello et al., 2016; He et al., 2016).

    PMID 27814488 DOI ↗

  19. SONAR Discovers RNA-Binding Proteins from Analysis of Large-Scale Protein-Protein Interactomes.

    Molecular cell · 2016 · 64(2): 282-293

    RNA metabolism is controlled by an expanding, yet incomplete, catalog of RNA-binding proteins (RBPs), many of which lack characterized RNA binding domains. Approaches to expand the RBP repertoire to discover non-canonical RBPs are currently needed. Here, HaloTag fusion pull down …

    PMID 27720645 DOI ↗

  20. Pairing beyond the Seed Supports MicroRNA Targeting Specificity.

    Molecular cell · 2016 · 64(2): 320-333

    To identify endogenous miRNA-target sites, we isolated AGO-bound RNAs from Caenorhabditis elegans by individual-nucleotide resolution crosslinking immunoprecipitation (iCLIP), which fortuitously also produced miRNA-target chimeric reads. Through the analysis of thousands of reproducible chimeras, pairing to the miRNA seed emerged as …

    PMID 27720646 DOI ↗

  21. Genomic analysis of the molecular neuropathology of tuberous sclerosis using a human stem cell model.

    Genome medicine · 2016 · 8(1): 94

    Tuberous sclerosis complex (TSC) is a genetic disease characterized by benign tumor growths in multiple organs and neurological symptoms induced by mTOR hyperfunction. Because the molecular pathology is highly complex and the etiology poorly understood, we employed a defined human …

    PMID 27655340 DOI ↗

  22. Rbfox2 function in RNA metabolism is impaired in hypoplastic left heart syndrome patient hearts.

    Scientific reports · 2016 · 6: 30896

    Hypoplastic left heart syndrome (HLHS) is a fatal congenital heart disease in which the left side of the heart is underdeveloped, impairing the systemic circulation. Underdeveloped left ventricle exerts biomechanical stress on the right ventricle that can progress into heart …

    PMID 27485310 DOI ↗

  23. Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses.

    Nature communications · 2016 · 7: 12143

    The RNA-binding protein (RBP) TAF15 is implicated in amyotrophic lateral sclerosis (ALS). To compare TAF15 function to that of two ALS-associated RBPs, FUS and TDP-43, we integrate CLIP-seq and RNA Bind-N-Seq technologies, and show that TAF15 binds to ∼4,900 RNAs …

    PMID 27378374 DOI ↗

  24. Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP).

    Nature methods · 2016 · 13(6): 508-14

    As RNA-binding proteins (RBPs) play essential roles in cellular physiology by interacting with target RNA molecules, binding site identification by UV crosslinking and immunoprecipitation (CLIP) of ribonucleoprotein complexes is critical to understanding RBP function. However, current CLIP protocols are technically …

    PMID 27018577 DOI ↗

  25. Dysregulation of RBFOX2 Is an Early Event in Cardiac Pathogenesis of Diabetes.

    Cell reports · 2016 · 15(10): 2200-2213

    Alternative splicing (AS) defects that adversely affect gene expression and function have been identified in diabetic hearts; however, the mechanisms responsible are largely unknown. Here, we show that the RNA-binding protein RBFOX2 contributes to transcriptome changes under diabetic conditions. RBFOX2 …

    PMID 27239029 DOI ↗