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. 2023 Aug 15;4(8):101160. doi: 10.1016/j.xcrm.2023.101160

Figure 5.

Figure 5

Lineage bias, increased cell apoptosis in mtUBA1 LymPs, and progressive loss of lymphocytic cells with differentiation

(A) Dynamic changes of LymP, GMP, and MEP ratios in VEXAS patients and healthy donors along pseudotime differentiation. x axis: pseudotime ordering from HSCs to LymP, GMP, and MEP, respectively, estimated by Palantir. y axis: Log2(percentages of corresponding cells in VEXAS patients) − log2(percentages of corresponding cells in healthy donors).

(B) Dynamic changes of lineage priming of HSCs to LymP, GMP, and MEP, along pseudotime differentiation. x axis: pseudotime ordering from HSCs to lineage-restricted progenitors estimated by Palantir. y axis: Log(lineage signature gene expression in patients/lineage signature gene expression in healthy donors). Lineage signature gene expression represented area under the receiver operating characteristic curve (AUC) values calculated with AUCell.

(C) Dynamic changes of expression levels of transcription factors (GATA1, SPI1, PAX5, CEBPA, and IRF8) along pseudotime differentiation. x axis: pseudotime ordering from HSCs to MEP, GMP, and LymP, respectively, estimated by Palantir. y axis: expression of transcription factors in patients normalized by that in healthy donors.

(D) A schematic diagram showing hematopoietic lineage specification and relative quantity of cell types in VEXAS patients and healthy donors.

(E) Dynamic changes of wtUBA1 LymP and mtUBA1 LymP ratios in HSPCs in VEXAS patients along differentiation. x axis: pseudotime ordering from HSCs to lineage-restricted progenitors estimated by Palantir. y axis: ratios of wtUBA1 LymP or mtUBA1 LymP in HSPCs.

(F) Dynamic changes of mtUBA1 cell ratios in LymP, GMP, and MEP in VEXAS patients along differentiation. x axis: pseudotime ordering from HSCs to lineage-restricted progenitors estimated by Palantir. y axis: Log(cell numbers of mutant/all HSPCs).

(G) Apoptosis gene expression scores (calculated by the AddModuleScore function in Seurat) of mtUBA1 cells normalized by wtUBA1 cells in myeloid and lymphoid BMMNCs were compared. y axis: normalized expression levels of apoptosis genes. A heatmap of apoptosis genes upregulated in mtUBA1 cells is shown on the right.