Fig. 3: Multiome analysis.

a, Integration, UMAP and cell populations of 10X multiome ATAC profiles from the Ts21 and disomic datasets. cDC, classical dendritic cell; MEMP, megakaryocyte–erythroid–mast progenitor; pDC, plasmacytoid dendritic cell. b, Circular projection of absorption probabilities for every HSC towards terminal states (using CellRank; left). Disomic HSCs are in blue, and Ts21 HSCs are in red. The proportion of HSCs differentiating towards the erythroid and megakaryocytic lineage (absorption probability > 0.5) with binomial test P values is also shown (right). c, UMAP with cells coloured according to RNA and ATAC similarity in disomic (left) and Ts21 (middle) HSCs, as estimated by the mutual information of RNA and ATAC topics in a single cell. The HSC latent UMAP space is characterized by a joint representation of both RNA and ATAC topic models (using MIRA). The UMAP space of all disomy and trisomy HSCs (n = 3,784 Ts21 and n = 2,431 disomic HSCs) is in grey. The boxplots represent the 25th, 50th and 75th percentiles, and the whiskers represent 1.5× the interquartile range. Significance was determined using a two-sided Mann–Whitney U-test. d, UMAP with cells coloured according to pseudotime. The arrows denote vectors of the directed cell transition matrix. e, Branches of HSC differentiation in the UMAP space (using MIRA). Cells are coloured by their probability of belonging to a specific branch. f, Compositional STREAM graph indicating abundances of disomic and Ts21 HSCs in each branch along pseudotime. The dashed line denotes half of the pseudotime.