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. 2021 Mar 8;12:1507. doi: 10.1038/s41467-021-21765-5

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — a A schematic of the classical hierarchy of human hematopoietic differentiation. b A UMAP dimensionality reduction of single-cell ATAC-seq profiles from 9974 FACS-isolated hematopoietic stem cells (HSCs). The colored points represent three 50-cell subsamples, each generated by selecting a single cell and identifying its nearest neighbors in principal component space. c A combined UMAP dimensionality reduction of single-cell ATAC-seq profiles from HSCs shown in (b) and 28,505 published bead-enriched CD34⁺ bone marrow progenitor cells¹⁷. The bead-enriched CD34⁺ cells are colored by the most correlated cell type from a FACS-isolated single-cell ATAC-seq reference²⁴. The box indicates the region containing FACS-isolated HSCs shown in (b), (d) and (e). d FACS-isolated HSCs colored by chromVAR transcription factor motif accessibility z-scores for GATA2. These scores represent enrichment or depletion of chromatin accessibility within peaks that contain the GATA2 motif (see Methods). e FACS-isolated HSCs colored by smoothed gene accessibility scores for MEF2C. These scores are a weighted sum of read counts within 10 kb of the MEF2C transcription start site, averaged over each cell’s 50 nearest neighbors (see Methods). f Aggregate chromatin accessibility signal tracks surrounding genes implicated as markers of lineage priming^24,29 for all 9974 FACS-isolated HSCs and the three denoised 50-cell subsamples of HSCs shown in (b). The arrows denote select regulatory regions with significant differences in chromatin accessibility relative to a random background. HSC: hematopoietic stem cell. MPP: Multipotent progenitor. LMPP: lymphoid-primed multipotent progenitor. CMP: common myeloid progenitor. CLP: common lymphoid progenitor. pDC: plasmacytoid dendritic cell. GMP: granulocyte-macrophage progenitor. MEP: megakaryocyte-erythroid progenitor. Source data are provided as a Source Data file.