scRNAseq from iPSC lines derived from a healthy donor and a DMD patient differentiated into the myogenic lineage
We previously demonstrated that iPSCs derived from a DMD patient and subjected to myogenic differentiation acquire a distinct transcriptomic profile from healthy controls. We observed a branched trajectory with an unbalanced distribution of Healthy and DMD cells on the two daughter branches. While each branch contained 86% of cells from a single line (either Healthy or DMD), we still observed 14% of cells from the other genetic background. This indicates that the choice between the two genetic states is probabilistic and does not strictly depend on the presence of the DMD mutation.  In the present study, we hypothesize that cell fate choice at the bifurcation point is governed by a GRN. To gain insight into the molecular events directly downstream of the mutation, we generated more resolutive scRNA-Seq data around the bifurcation point. We subjected WT and mutant iPS cells to directed myogenic differentiation and we used Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-Seq) to barcode cells collected at 8 time points spanning the bifurcation window between Day 5 and Day 14.
We previously demonstrated that iPSCs derived from a DMD patient and subjected to myogenic differentiation acquire a distinct transcriptomic profile from healthy controls. We observed a branched trajectory with an unbalanced distribution of Healthy and DMD cells on the two daughter branches. While each branch contained 86% of cells from a single line (either Healthy or DMD), we still observed 14% of cells from the other genetic background. This indicates that the choice between the two genetic states is probabilistic and does not strictly depend on the presence of the DMD mutation.  In the present study, we hypothesize that cell fate choice at the bifurcation point is governed by a GRN. To gain insight into the molecular events directly downstream of the mutation, we generated more resolutive scRNA-Seq data around the bifurcation point. We subjected WT and mutant iPS cells to directed myogenic differentiation and we used Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-Seq) to barcode cells collected at 8 time points spanning the bifurcation window between Day 5 and Day 14.
European Bioinformatics Institute