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. 2022 Jun 25;5:626. doi: 10.1038/s42003-022-03591-7

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© The Author(s) 2022

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. 6 — a In vivo validation of StemLeish signature in three independent cohorts of human VL patients from Brazil, from India and HIV-VL co-infected patients from Ethiopia, all fold-changes of DEG from untreated patients with active disease vs. post-treatment blood samples. Venn diagram (upper left panel) shows overlap between murine and human signatures. Human Phenotype Ontology (MSigDb) enrichment analysis indicates the StemLeish signature phenocopies the complete clinical picture of human VL (lower left panel). Significant correlations (Spearman) between StemLeish and human VL DEG in all three cohorts (right panel). b Integrated epigenetic, transcriptomic and genomic analysis of the Rgs1 locus, visualized in UCSC Gene browser. Open chromatin regions (DNase I Hypersensitive Sites) in purified CD34⁺HSC (indicated as CD34⁺) and HSC undergoing myeloid differentiation (indicated as CD34⁻) are indicated by light blue shades. Transcriptomic data (RNAseq) represent mapped reads present in purified CD14⁺ vs. purified mobilized CD34⁺ cells, with embryonic stem cells (ESC) and lymph node RNAseq data plotted for comparison. Genomic data show conservation score across 100 different vertebrate species (blue: conserved, brown: not conserved), with leishmaniasis and tuberculosis model species (rhesus macaques, mouse, hamster, dog, zebrafish) plotted individually (green panels below), as compared to the human reference genome. c Reanalysis of single-cell RNAseq data⁵⁰ using UMAP (Unifold Mapping) revealed presence within purified human CD34⁺ cells of an RGS1^high phenotype in several progenitor subsets [Erythro-Myeloid Progenitors (EMP), Lymphoid/Myeloid Progenitors (LMPP7), HSC in a metabolically active state (HSC/Met. state)]. Arrows demonstrate clusters containing RGS1^high cells (orange vs. gray RGS1^low cells). Arrow sizes are proportional to the frequency of RGS1^high cells. Clipart used in diagram (a) was obtained from Servier Medical Art (https://smart.servier.com).