There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Human hematopoiesis involves cellular differentiation of multipotent cells into progressively
more lineage-restricted states. While the chromatin accessibility landscape of this
process has been explored in defined populations, single-cell regulatory variation
has been hidden by ensemble averaging. We collected single-cell chromatin accessibility
profiles across 10 populations of immunophenotypically defined human hematopoietic
cell types and constructed a chromatin accessibility landscape of human hematopoiesis
to characterize differentiation trajectories. We find variation consistent with lineage
bias toward different developmental branches in multipotent cell types. We observe
heterogeneity within common myeloid progenitors (CMPs) and granulocyte-macrophage
progenitors (GMPs) and develop a strategy to partition GMPs along their differentiation
trajectory. Furthermore, we integrated single-cell RNA sequencing (scRNA-seq) data
to associate transcription factors to chromatin accessibility changes and regulatory
elements to target genes through correlations of expression and regulatory element
accessibility. Overall, this work provides a framework for integrative exploration
of complex regulatory dynamics in a primary human tissue at single-cell resolution.