Investigating Human Foetal Blood Development at the Single Cell Level

Regulation of hematopoiesis during human development remains poorly defined. We have applied single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) to human immunophenotypic blood cells from fetal liver and bone marrow. Integrative analysis of chromatin accessibility and gene expression revealed extensive epigenetic —but not transcriptional— priming of HSCs/MPPs prior to their lineage commitment. In the next set of experiments, we reconstructed a phylogenetic tree of blood development using whole-genome sequencing of single-cell-derived hematopoietic colonies from healthy human fetuses, coupled with deep targeted sequencing of tissues of known embryonic origin. We found that in healthy fetuses, individual hematopoietic progenitors acquire tens of somatic mutations by 18 weeks after conception. We used these mutations as barcodes and timed the divergence of embryonic and extra-embryonic tissues during development, and estimated the number of blood antecedents at different stages of embryonic development. By Attending You Will: - Learn how integration of scRNA-seq and scATAC-Seq datasets can be utilised to address the questions related with cell fate choices in the context of blood development. - Discover about ways to improve sorting strategy for cells of interest using information obtained from scRNA-Seq data. - Find out how somatic mutations can be used to lineage-trace human development.