Abstract

Genome-wide transcriptome profiling of the bulk mixture of cells is not ideal for identifying RNA or proteomic signatures that are dysfunctional in Autism spectrum disorder relative to normal genotypes in patient-derived cells. The objective of Project 3 is to develop computational and experimental workflows to identify disease- associated differences at the single-cell level from heterogeneous mixtures of cortical neurons and glial cells. We will perform multi parameter optimization and test our experimental workflow for transparency and robustness. We will apply our optimized workflows to autism-specific hIPSC models from Project 1 to identify disease-specific, cell-type specific RNA signatures.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19MH107367-02
Application #
9146983
Study Section
Special Emphasis Panel (ZMH1)
Project Start
Project End
Budget Start
2016-07-01
Budget End
2017-06-30
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost

  Institution

Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Mesci, Pinar; Macia, Angela; LaRock, Christopher N et al. (2018) Modeling neuro-immune interactions during Zika virus infection. Hum Mol Genet 27:41-52
Chailangkarn, Thanathom; Noree, Chalongrat; Muotri, Alysson R (2018) The contribution of GTF2I haploinsufficiency to Williams syndrome. Mol Cell Probes 40:45-51
Brito, Anita; Russo, Fabiele Baldino; Muotri, Alysson Renato et al. (2018) Autism spectrum disorders and disease modeling using stem cells. Cell Tissue Res 371:153-160
Fernandes, Isabella R; Cruz, Ana C P; Ferrasa, Adriano et al. (2018) Genetic variations on SETD5 underlying autistic conditions. Dev Neurobiol 78:500-518
Mesci, Pinar; Macia, Angela; Moore, Spencer M et al. (2018) Blocking Zika virus vertical transmission. Sci Rep 8:1218
Beltrão-Braga, Patricia C B; Muotri, Alysson R (2017) Modeling autism spectrum disorders with human neurons. Brain Res 1656:49-54
Song, Yan; Botvinnik, Olga B; Lovci, Michael T et al. (2017) Single-Cell Alternative Splicing Analysis with Expedition Reveals Splicing Dynamics during Neuron Differentiation. Mol Cell 67:148-161.e5
de Souza, Janaina S; Carromeu, Cassiano; Torres, Laila B et al. (2017) IGF1 neuronal response in the absence of MECP2 is dependent on TRalpha 3. Hum Mol Genet 26:270-281
Shiryaev, Sergey A; Mesci, Pinar; Pinto, Antonella et al. (2017) Repurposing of the anti-malaria drug chloroquine for Zika Virus treatment and prophylaxis. Sci Rep 7:15771
Kakaradov, Boyko; Arsenio, Janilyn; Widjaja, Christella E et al. (2017) Early transcriptional and epigenetic regulation of CD8+ T cell differentiation revealed by single-cell RNA sequencing. Nat Immunol 18:422-432

Showing the most recent 10 out of 17 publications