William Greenleaf, PhD
Associate Professor of Genetics
Stanford University
Single-cell epigenomics maps the continuous regulatory landscape of human hematopoietic differentiation
Normal human hematopoiesis involves cellular differentiation of multipotent cells into progressively more lineage-restricted states. While epigenomic landscapes of this process have 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 an epigenomic landscape of human hematopoiesis to characterize differentiation trajectories. We find epigenomic variation consistent with lineage-bias toward different developmental branches in multipotent cell-types. We identify and isolate sub-populations within granulocyte-macrophage progenitors (GMPs) and confirm that GMPs are epigenomically and transcriptomically heterogeneous. Furthermore, we integrated scRNA-seq data to link transcription factors to epigenomic changes, as well as link regulatory elements to target genes through correlations of expression and regulatory element accessibility. Overall, this work provides a resource for integrative exploration of complex regulatory dynamics in primary human tissues at the ultimate level of granular specificity – the single-cell.
Jason D Buenrostro1,2, M Ryan Corces3, Caleb A Lareau1, Beijing Wu4, Alicia N Schep4, Martin Aryee1, Ravindra Majeti5,6, Howard Y. Chang3, William J. Greenleaf3,4,7,8
1Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
2Harvard Society of Fellows, Harvard University, Cambridge, MA 02138, USA.
3Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
4Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
School of Medicine, Stanford, CA 94305, USA.
5Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
6Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
7Department of Applied Physics, Stanford University, Stanford, CA 94025, USA.
8Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
