Journal: Nature Communications

Article Title: Severe inflammation and lineage skewing are associated with poor engraftment of engineered hematopoietic stem cells in patients with sickle cell disease

doi: 10.1038/s41467-025-58321-4

Figure Lengend Snippet: The Cell-ID method was used to assess the statistical enrichment of individual-cell gene signatures vs. signaling pathway gene sets (such as Hallmark gene sets, MSigDB collections, v7.5.1) based on two-sided hypergeometric test p -values with Benjamini–Hochberg correction for the number of tested gene signatures. Enrichment scores were calculated as the -log10( p -value). a UMAP plots highlighting cells significantly matching the All HSC and MkP signatures, for each HD ( n = 3) and SCD patient ( n = 3) ( p < 0.05). Cells matching All HSC and MkP cell types are shown in black, and cells matching with only one cell type are shown in red (All HSC) and pink (MkP). The number of cells in each category and per patient, is depicted in the histogram on the right. b Boxplots of IL1 β and VWF mRNA expression in HSCs, HSC-enriched and MkP populations, in each HD ( n = 3) and SCD patient ( n = 3). c , d UMAP plots of TNFa and IFN gamma response pathway enrichment scores for each HD ( n = 3) and SCD patient ( n = 3), determined with Cell-ID. e , f Boxplots representing significant TNFa and IFN gamma enrichment scores ( p < 0.01) in HSCs for each HD ( n = 3) and SCD patient ( n = 3). Dotted lines represent the significant threshold -log 10 ( p -value = 0.01). g , h Boxplot representing CEBPB, MAFF, IFI44L , and MX1 mRNA expression in the HSCs populations in each HD ( n = 3) and SCD patient ( n = 3). In each boxplot, the edges of the box indicate the first and third quartiles and the center line indicates the data median. The whiskers denote 1.5× interquartile range, data beyond the end of the whiskers are called “outlying” points and are plotted individually.

Article Snippet: Briefly, RBC samples frozen in glycerol were thawed, fixed and permeabilized before being incubated with mouse monoclonal antibodies (Ab) against human γ-globin chain (IQ Products: IQP-363-INT-4), β S -globin chain (Rockland: 200-301-GS5) or βA-globin chain (Rockland: 200-301-GS4).

Techniques: Expressing