Integrated PhD Student Indian Institute of Science (IISc), Bengaluru Bengaluru, Karnataka, India
Abstract: Recent studies based on allele-specific RNA-sequencing analysis revealed clonal random monoallelic expression (clonal RME) of autosomal genes in different cell types. Clonal RME represents stable maintenance of paternal-monoallelic or maternal-monoallelic expression of genes in specific clonal cell populations, along with stable biallelic expression in other clones. Thus, clonal RME creates stable yet heterogeneous allelic expression patterns within a particular cell type. Considering the potential of clonal RME in shaping heterogenous gene expression during early embryonic development, we wondered whether clonal RME contributes to the dynamic cell fate transitions. To address this, we have profiled the clonal RME landscape in early embryonic lineages, namely extraembryonic endoderm (XEN) stem cells, trophoblast stem cells (TSC) and epiblast stem cells (EpiSC) through allele-specific RNA-sequencing analysis. Importantly, our genome-wide analysis revealed that the majority of the RME genes in XEN, TSC and EpiSC were lineage-specific. Interestingly, we found only a few common RME genes across XEN, TSC and EpiSC, all of which are highly crucial for early embryonic development. Furthermore, our preliminary analysis depicts that the clonal RME landscape gets altered with cell state transition in XEN cells, suggesting the plausible relevance of clonal RME in cell fate specification. Separately, we also found that clonal RME is stable across multiple passages in the XEN cells. Altogether, we delineate that stable clonal RME might quantitatively fine-tune gene expression dosage to drive cell fate specification events during early embryonic development. These findings could foster the broader understanding of how clonal RME may contribute to gene expression variability potentially influencing the incomplete penetrance and variable expressivity of autosomal disorders.
