Summary

Regulation of hematopoiesis during human development remains poorly defined. Here we applied single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) to over 8,000 human immunophenotypic blood cells from fetal liver and bone marrow. We inferred their differentiation trajectory and identified three highly proliferative oligopotent progenitor populations downstream of hematopoietic stem cells (HSCs)/multipotent progenitors (MPPs). Along this trajectory, we observed opposing patterns of chromatin accessibility and differentiation that coincided with dynamic changes in the activity of distinct lineage-specific transcription factors. Integrative analysis of chromatin accessibility and gene expression revealed extensive epigenetic but not transcriptional priming of HSCs/MPPs prior to their lineage commitment. Finally, we refined and functionally validated the sorting strategy for the HSCs/MPPs and achieved around 90% enrichment. Our study provides a useful framework for future investigation of human developmental hematopoiesis in the context of blood pathologies and regenerative medicine.

Overall design

This is plate-based (SmartSeq2-Seq) single-cell transcriptome data set from 15 human foetal livers and bone marrow (17-22 PCW). It includes 5,867 cells with an average of 3,074 genes per cell before QC and 4,504 cells with an average of 3,642 genes per cell after QC.This is plate-based chromatin accessibility data set from 3 human foetal livers and bone marrow (18-21 PCW). It includes 4,001 cells before QC and 3,611 cells after QC.

Contributors

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Contact

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