The main objective of Project 2 is to identify and characterize cortical neurons from layer V and subtypes of astrocytes derived from human induced pluripotent stem cells (iPSCs) and measure their contribution to Autism Spectrum Disorders (ASD). Pyramidal neurons from cortical layer V are linked to primate social behavior and human-related conditions, such as ASD and Williams syndrome (WS). Glia cells have historically played a secondary role in neuroscience but recent data indicating a major contribution of astrocytes to several human neurological disorders has challenged this view. Thus, we propose to apply the design of experiments (DOE), a powerful statistical tool, to improve the differentiation protocols for cortical neurons layer V and astrocytes derived from iPSCs. These will be applied to engineered lines from Project 1 for molecular and cellular assays in the Projects 3, 4 and 5.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19MH107367-02
Application #
9146982
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
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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
Herai, Roberto H; Negraes, Priscilla D; Muotri, Alysson R (2017) Evidence of nuclei-encoded spliceosome mediating splicing of mitochondrial RNA. Hum Mol Genet 26:2472-2479
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

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