Extended Data Fig. 8: Extended spatial transcriptomic analysis of PSC-CM and RA-PSC-CM grafts, and surrounding pig myocardium. | Nature Cardiovascular Research

Extended Data Fig. 8: Extended spatial transcriptomic analysis of PSC-CM and RA-PSC-CM grafts, and surrounding pig myocardium.

From: Cellular heterogeneity of pluripotent stem cell-derived cardiomyocyte grafts is mechanistically linked to treatable arrhythmias

Extended Data Fig. 8

(a) Separation of human and pig spots by principal component analysis, using all genes as input. (b) Thresholding for human spots ( > 50 human genes) highly correlates with immunofluorescent staining of GFP+ human PSC-CM graft. (c) Unbiased clustering of human PSC-CM and RA-PSC-CM (d) spots and relative expression of cardiomyocyte-associated and other relevant genes (e). (f) Pseudobulk differential gene expression between PSC-CM and RA-PSC-CM graft shows upregulation of pan-cardiomyocyte and ventricular genes (ACTN2, TNNI1, TNN13, MYH7, MYL2) in PSC-CM graft and upregulation of atrial and pacemaker associated genes, calcium handling, and extracellular matrix genes (NPPA, MYH6, CALM2, ELN) in RA-PSC-CM graft. g) Integrated analysis/deconvolution of spatial transcriptomic and scRNAseq datasets shows location of cell subclusters within PSC-CM and RA-PSC-CM grafts. (h) The test of equal or given proportions confirmed the presence of engraftment arrhythmia-causing atrial and pacemaker-like subcluster myocytes were found to be located entirely within the RA-PSC-CM graft.

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