Fig. 5: The functional link among telomere shortening, IFN signaling activation, and HSC differentiation towards the megakaryocyte lineage is conserved in humans.
From: Hematopoiesis under telomere attrition at the single-cell resolution
a UMAP of scRNA-seq data displaying single Lin−CD34+ cells isolated from two healthy donors (HDs; n = 3800) and two individuals with a pathological TERT mutation (TERTmut; n = 4105). Each dot represents one cell. The sample origin (left) and cluster identity (middle) of each cell are indicated by different colors. Right, distribution of the HD and TERTmut Lin−CD34+ cells among clusters defined by distinct lineage differentiation profiles. b Pathway enrichment analysis of significantly upregulated genes in TERT-mutant HSCs from cluster 1 shown in Fig. 5a as compared with those of HDs (adjusted P ≤ 0.05). The top ten Hallmark and Reactome gene sets are shown. c UMAP of scATAC-seq data displaying 4546 and 3489 single Lin−CD34+ cells isolated from one HD and one individual with a pathological TERT mutation, respectively. Each dot represents one cell. The sample origin (left) and cluster identity (right) of each cell are indicated by different colors. d Dot plot of the level of activities of the top ten TFs whose binding sites were significantly enriched in the open chromatin regions of TERT-mutant cells from cluster 3 shown Fig. 5c as compared to those enriched in the open chromatin regions of HD cells. e UMAP of scRNA-seq data displaying single Lin−CD34+ cells isolated from two HDs (n = 1958 cells) and two patients with pathogenic telomerase complex mutations and severe BM failure syndrome (TERT/TERCmut; n = 856 cells). Each dot represents one cell. The sample (left) and cluster (middle) identities are indicated by different colors. Right, the distribution of the HD and Lin−CD34+ cells among clusters is defined by distinct lineage differentiation profiles. HSC hematopoietic stem cell, MPP multipotent progenitor, Baso basophil, Meg megakaryocytic, Ery erythroid, Myelo myeloid, Lympho lymphoid, DC dendritic cells. Source data are provided as a Source Data file.
