Year: 2020
Type: preprint
Abstract: Joint profiling of transcriptome and chromatin accessibility within single cells allows for the deconstruction of the complex relationship between transcriptional states and upstream regulatory programs determining different cell fates. Here, we developed an automated method with high sensitivity, assay for single-cell transcriptome and accessibility regions (ASTAR-seq), for simultaneous measurement of whole-cell transcriptome and chromatin accessibility within the same single cell. To show the utility of ASTAR-seq, we profiled 384 mESCs under naive and primed pluripotent states as well as a two-cell like state, 424 human cells of various lineage origins (BJ, K562, JK1, and Jurkat), and 480 primary cord blood cells undergoing erythroblast differentiation. With the joint profiles, we configured the transcriptional and chromatin accessibility landscapes of discrete cell states, uncovered linked sets of cis -regulatory elements and target genes unique to each state, and constructed interactome and transcription factor (TF)–centered upstream regulatory networks for various cell states.
Source: Genome Research
Institutions: Agency for Science, Technology and Research, Nanyang Technological University, Institute of Molecular and Cell Biology, National University of Singapore, Broad Institute, Harvard University, Wyss Institute for Biologically Inspired Engineering, Massachusetts Institute of Technology, Radboud University Nijmegen, Mayo Clinic
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Funders: Glenn Foundation for Medical Research, National Research Foundation, Agency for Science, Technology and Research, National Research Foundation Singapore, Fondation pour la Recherche Médicale, National Institutes of Health, Center for Individualized Medicine, Mayo Clinic, Medical Research Council, National Medical Research Council, Biomedical Research Council, National Institute on Aging, National Cancer Institute
Awards: G4440839649, G4903442668, Capturing the molecular complexity of Alzheimer's disease through the lens of RNA binding proteins, G660031745, G685890680, G7116006866, Determinants of pancreatic cancer and malignant melanoma phenotypes in CDKN2A hereditary kindreds, Harnessing Molecular Networks of Resilience for Therapeutic Discoveries in AD, G7877397355, G8407492312, G947014966
OpenAlex ID: W3044262883