Single-cell joint detection of chromatin occupancy and transcriptome enables higher-dimensional epigenomic reconstructions.
Nat Methods
; 18(6): 652-660, 2021 06.
Article
in En
| MEDLINE
| ID: mdl-33958790
ABSTRACT
Deciphering mechanisms in cell-fate decisions requires single-cell holistic reconstructions of multidimensional epigenomic states in transcriptional regulation. Here we develop CoTECH, a combinatorial barcoding method allowing high-throughput single-cell joint detection of chromatin occupancy and transcriptome. We used CoTECH to examine bivalent histone marks (H3K4me3 and H3K27me3) with transcription from naive to primed mouse embryonic stem cells. We also derived concurrent bivalent marks in pseudosingle cells using transcriptome as an anchor for resolving pseudotemporal bivalency trajectories and disentangling a context-specific interplay between H3K4me3/H3K27me3 and transcription level. Next, we revealed the regulatory basis of endothelial-to-hematopoietic transition in two waves of hematopoietic cells and distinctive enhancer-gene-linking schemes guiding hemogenic endothelial cell emergence, indicating a unique epigenetic control of transcriptional regulation for hematopoietic stem cell priming. CoTECH provides an efficient framework for single-cell coassay of chromatin occupancy and transcription, thus enabling higher-dimensional epigenomic reconstructions.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chromatin
/
Single-Cell Analysis
/
Epigenomics
/
Transcriptome
Type of study:
Diagnostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Nat Methods
Journal subject:
TECNICAS E PROCEDIMENTOS DE LABORATORIO
Year:
2021
Document type:
Article
Affiliation country:
China