Fig. 4: Age-dependent HSPC–stromal interactions are linked to LyP lineage bias. | Nature Immunology

Fig. 4: Age-dependent HSPC–stromal interactions are linked to LyP lineage bias.

From: Single-cell multiomic atlas of healthy pediatric bone marrow reveals age-dependent differences in lineage differentiation driven by stromal signaling

Fig. 4

a, NicheNet interaction analysis of differential interactions between LyP-B (n = 690 cells) and LyP-S (n = 649 cells) cells in CITE-seq data from BM aspirates of YP and AYA donors combined (n = 9; 2.1–31.3 years, three male, six female donors; Supplementary Table 1), showing the top three predicted ligands underlying the observed upregulation of LyP-B cell genes (top rows) and LyP-S cell genes (bottom rows), prioritized based on regulatory potential and differential receptor expression between the two LyP cell subsets. The genes shown represent the top 30 differentially expressed genes in LyP-B (left) or LyP-S (right) cells predicted to be regulated by these ligands. The regulatory potential of LyP-B cell ligands on LyP-S cell genes (top right quadrant) and vice versa (bottom left quadrant) is also shown. b, Dot plot showing the average expression of IL7R, IL2RG, TGFBR1 and TGFBR2 in LyP-B and LyP-S cell subsets (IL7R (LyP-B versus LyP-S; FC: 7.01, P < 0.001), IL2RG (LyP-B versus LyP-S; FC: 1.45, P = 0.002) and TGFBR1 (LyP-S versus LyP-B; FC: 2.26, P < 0.001; two-sided Wilcoxon rank-sum test with Benjamini–Hochberg false discovery rate correction)). Dot color indicates scaled receptor expression, and dot size represents the percentage of expressing cells. c–e, Dot plot showing the average mRNA expression of IL7 and TGFB1 in all BM cell types from CITE-seq data (c), in all BM cell types combined per individual (d) and in MSC only per individual (e). f, Box plots showing the concentrations of IL-7, IL-3, IL-15 and IL-34 protein measured by multiplex immunoassay (LegendPlex) in the BM of 78 individuals (age range of 0–20, median age of 8 years, 47 male and 31 female donors; Supplementary Table 13) with localized solid tumors without BM involvement. Boxes represent the median and the first and third quartiles, and whiskers indicate data points within 1.5 times the interquartile range. P values were calculated using a two-sided Wilcoxon rank-sum test.

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