Genomic Architecture of Cells in Tissues (GeACT): Study of Human Mid-gestation Fetus
Summary
By circumventing cellular heterogeneity, single cell omics have now been widely utilized for cell typing in human tissues, culminating with the undertaking of human cell atlas aimed at characterizing all human cell types. However, more important are the probing of gene regulatory networks, underlying chromatin architecture and critical transcription factors for each cell type. Here we report the Genomic Architecture of Cells in Tissues (GeACT), a comprehensive genomic data base that collectively address the above needs with the goal of understanding the functional genome in action. GeACT was made possible by our novel single-cell RNA-seq (MALBAC-DT) and ATAC-seq (METATAC) methods of high detectability and precision. We exemplified GeACT by first studying representative organs in human mid-gestation fetus. In particular, correlated gene modules (CGMs) are observed and found to be cell-type-dependent. We linked gene expression profiles to the underlying chromatin states, and found the key transcription factors for representative CGMs.
Highlights
Genomic Architecture of Cells in Tissues (GeACT) data for human mid-gestation fetus
Determining correlated gene modules (CGMs) in different cell types by MALBAC-DT
Measuring chromatin open regions in single cells with high detectability by METATAC
Integrating transcriptomics and chromatin accessibility to reveal key TFs for a CGM
Competing Interest Statement
A.R.C., D.F.L., and X.S.X. are inventors on the patent PCT/US18/34689 filed by President and Fellows of Harvard College that covers MALBAC-DT. L.T., D.X., and X.S.X. are inventors on a patent WO2018217912A1 filed by President and Fellows of Harvard College that covers METATAC.
Footnotes
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