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X-WR-CALNAME:Chromatin Modifiers In Autism and Combining Pooled CRISPR Scre
 ens with Single-Cell Chromatin Accessibility Profiling
X-WR-TIMEZONE:Eastern Time (US & Canada)
BEGIN:VEVENT
DTSTAMP:20260520T163514Z
UID:tag:localist.com\,2008:EventInstance_31707041428002
DTSTART:20191204T210000Z
DTEND:20191204T220000Z
DESCRIPTION:SCSB Colloquium Series\n\nWednesday\, December 4\, 2019\nTime: 
 4:00 pm-5:00 pm\, followed by reception\nSpeaker: Neville Sanjana\, Ph.D.\
 n\nHost: Feng Zhang\, Ph.D.\n\nAffiliation: Core Faculty Member\, New York
  Genome Center\; Assistant Professor of Biology\, Neuroscience and Physiol
 ogy\, New York University\n\nTalk title: Chromatin modifiers in autism and
  combining pooled CRISPR screens with single-cell chromatin accessibility 
 profiling\n\nAbstract: One of the most commonly mutated genes in autism is
  the chromatin remodeler CHD8. Despite the prevalence of CHD8 mutations\, 
 we have little insight into how CHD8 loss impacts genome organization and 
 the functional consequences of these molecular alterations in neurons. Her
 e\, we combine gene editing in human pluripotent stem cells and rapid cort
 ical neuron differentiation to create an isogenic model of CHD8 loss in ne
 urons. By measuring changes in chromatin accessibility and gene expression
 \, we identified hundreds of genes with altered expression\, including man
 y involved in neural development and excitatory synaptic transmission. Usi
 ng field recordings and single-cell electrophysiology\, we found a 3-fold 
 decrease in firing rates and synaptic activity in CHD8+/– neurons. We al
 so observed a similar firing rate deficit in primary cortical neurons from
  CHD8+/– mice. These alterations in neuron and synapse function after CH
 D8 hemizygous loss can be rescued by CHD8 overexpression.\n\nGiven CHD8’
 s role in chromatin remodeling\, we used the assay of transposable and acc
 essible chromatin sequencing (ATAC-seq) to map changes in open chromatin g
 enome-wide. In differentiated human neurons\, we found that CHD8 hemizygou
 s loss results in a large increase in open chromatin across the genome wit
 h the greatest change in compaction near the gene Autism Susceptibility Ca
 ndidate 2 (AUTS2)\, a transcriptional regulator that has previously been i
 mplicated in autism.\n\nIn the last part of my talk\, I’ll address the c
 hallenge of scaling up this approach: CHD8 is just one gene and many diffe
 rent chromatin remodeling and modifying enzymes have been implicated in au
 tism. To address this\, we recently developed a scalable\, cost-effective 
 method called CRISPR-sciATAC that links genome-wide chromatin accessibilit
 y to genetic perturbations through simultaneous capture and barcoding of A
 TAC-seq fragments and CRISPR guide RNAs. Using a species-mixing experiment
 \, we show that CRISPR-sciATAC results in a low doublet rate. Finally\, we
  use CRISPR-sciATAC to knock-out 21 different chromatin modifiers and gene
 rate chromatin accessibility data from ~12\,000 single cells.\n\nPublicati
 ons: http://sanjanalab.org/papers.html
GEO:42.362302;-71.091766
LOCATION:Building 46\, 46-3002\, Singleton Auditorium\, 3rd floor
SUMMARY:Chromatin Modifiers In Autism and Combining Pooled CRISPR Screens w
 ith Single-Cell Chromatin Accessibility Profiling
URL;VALUE=URI:https://calendar.mit.edu/event/scsb_colloquium_series_neville
 _sanjana_phd_new_york_genome_center_new_york_university
CATEGORIES:Conferences/Seminars/Lectures
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