How distinct transcriptional programs are enacted to generate cellular heterogeneity and plasticity,and enable complex fate decisions are important open questions.One key regulator is the cell’s epigenome state that ...How distinct transcriptional programs are enacted to generate cellular heterogeneity and plasticity,and enable complex fate decisions are important open questions.One key regulator is the cell’s epigenome state that drives distinct transcriptional programs by regulating chromatin accessibility.Genome-wide chromatin accessibility measurements can impart insights into regulatory sequences(in)accessible to DNA-binding proteins at a single-cell resolution.This review outlines molecular methods and bioinformatic tools for capturing cell-to-cell chromatin variation using single-cell assay for transposase-accessible chromatin using sequencing(scATAC-seq)in a scalable fashion.It also covers joint profiling of chromatin with transcriptome/proteome measurements,computational strategies to integrate multi-omic measurements,and predictive bioinformatic tools to infer chromatin accessibility from single-cell transcriptomic datasets.Methodological refinements that increase power for cell discovery through robust chromatin coverage and integrate measurements from multiple modalities will further expand our understanding of gene regulation during homeostasis and disease.展开更多
基金a Cancer Research Society award(Scholarships for the New Generation of Scientists).NJB was supported by Multiple Myeloma Research Foundation.ATS was supported by the National Institutes of Health(NIHGrant No.K08CA230188)+2 种基金the Parker Institute for Cancer Immunotherapy,a Cancer Research Institute Technology Impact Award,a Career Award for Medical Scientists from the Burroughs Wellcome Fund,and the Human Vaccines Project Michelson Prize.HJ and WZ were supported by the National Human Genome Research Institute of NIH(Grant Nos.R01HG009518 and R01HG010889)JAS was supported by an Alberta Children’s Hospital Research Institute Postdoctoral Fellowship.AJ was supported by an Alberta Innovates Summer Studentship.JB was supported by Canadian Institutes of Health Research(PJT-401394)Calgary Firefighters Burn Treatment Society.
文摘How distinct transcriptional programs are enacted to generate cellular heterogeneity and plasticity,and enable complex fate decisions are important open questions.One key regulator is the cell’s epigenome state that drives distinct transcriptional programs by regulating chromatin accessibility.Genome-wide chromatin accessibility measurements can impart insights into regulatory sequences(in)accessible to DNA-binding proteins at a single-cell resolution.This review outlines molecular methods and bioinformatic tools for capturing cell-to-cell chromatin variation using single-cell assay for transposase-accessible chromatin using sequencing(scATAC-seq)in a scalable fashion.It also covers joint profiling of chromatin with transcriptome/proteome measurements,computational strategies to integrate multi-omic measurements,and predictive bioinformatic tools to infer chromatin accessibility from single-cell transcriptomic datasets.Methodological refinements that increase power for cell discovery through robust chromatin coverage and integrate measurements from multiple modalities will further expand our understanding of gene regulation during homeostasis and disease.
