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. 2024 Oct 30;636(8041):241–250. doi: 10.1038/s41586-024-08137-x

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, 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 licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

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Fig. 2 — a, Experimental scheme. CB CD34⁺ cells were transduced with lentiviral vectors as indicated and analysed by flow cytometry (right panels) on the day of transplantation, that is, 7 days after the first transduction (day 8). b, Uniform manifold approximation and projection (UMAP) representation of integrated single-cell transcriptome data from the six groups of cells shown in a, on day 8. c, Stacked barplots showing fraction of cells in each cluster. With the exception of clusters marked as not significant (NS), all other cluster sizes were significantly different from the respective cluster size in the Ctrl (mCherry/GFP) group (logistic regression). d, iPS-HSPCs with NRAS (R) or SRSF2 and ASXL1 mutations (SA) were transduced with lentiviral vectors as indicated. Right panels, principal component analysis of RNA-seq and ATAC-seq data from sorted CD34⁺CD45⁺ cells; n = 3 independent experiments for all groups. e, Normalized enrichment scores (NES) and adjusted P values derived from gene set enrichment analysis (GSEA) for gene sets corresponding to the human AML developmental hierarchy from ref. ¹⁴ using gene lists ranked by the −log₁₀(P_adjusted (padj)) × log₂FC from the indicated differential expression comparisons. f, Heatmap showing Pearson correlation values for the ATAC-seq peak normalized read counts in the iPS-HSPC dataset from d and overlapping peaks in primary normal haematopoietic cell subpopulations from ref. ²⁹. g, Experimental scheme (left) and survival (right) of animals transplanted with CMPs and GMPs transduced with SA and sorted prior to induction of R with Dox. n = 1 for each CMP group (±Dox); n = 3 for each GMP group (±Dox). h, Experimental scheme (left) and survival (right) of mice transplanted with CMPs and GMPs sorted prior to SAR transduction. n = 4 for all groups. i, FACS-sorted CMPs and GMPs from g. CLP, common lymphoid progenitor; DC P, dendritic cell progenitor; EBM, eosinophil/basophil/mast cell; Ery/Meg P, erythrocyte/megakaryocyte progenitor; Ery P, erythrocyte progenitor; LMPP, lymphoid-primed MPP; Meg P, megakaryocyte progenitor; Mono, monocyte; Mono P, monocyte progenitor; ProMono, promonocyte.

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