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Bengaluru: Indian Institute of Science (IISc) researchers have uncovered new details about how genes are expressed during the reprogramming of adult cells into induced pluripotent stem cells (iPSCs).
Their study, published in Nature Genetics, reveals the role of coordinated gene expression from both the maternal and paternal copies of genes in driving this process and researchers feel the new insights could help optimise protocols for generating iPSCs for therapeutic applications.
“iPSCs have emerged as a powerful tool for studying development and disease, as they can theoretically give rise to any cell type in the body. However, molecular mechanisms behind generating iPSCs by reprogramming other cell types remains incompletely understood. Our team, led by Srimonta Gayen, used single-cell RNA sequencing to analyse gene expression patterns as mouse embryonic fibroblasts were reprogrammed into iPSCs,” IISc researchers said.
It added that the team focused on dynamics of “transcriptional bursting” – how genes sporadically ramp up RNA production — and surprisingly found that while most genes showed semi-coordinated bursting between their two gene copies (alleles), some exhibited highly synchronised bursting of both alleles simultaneously.
Genes involved in key reprogramming pathways, like pluripotency and protein production, were enriched in this highly coordinated group.
“Our findings suggest that coordinating the expression levels of these two alleles is an important way of precisely controlling the gene dosages required for successful reprogramming,” says Gayen.
Researchers at IISc showed that differences in chromatin accessibility between alleles underlie their varying levels of coordination during transcriptional bursting. By adjusting DNA packaging, the cell can facilitate or restrict simultaneous expression from both gene copies.
