Pang, C. N. I. | Search bioRxiv

bioRxiv2024

Unraveling the Role of MIXL1 Activation in Endoderm Differentiation of Isogenic Human Induced Pluripotent Stem Cells

Human induced pluripotent stem cells (hiPSC) possess the ability to differentiate into a multitude of cell and tissue types but display heterogeneous propensity of differentiation into specific lineage. Characterization of the transcriptome of eleven hiPSC lines showed that activation of MIXL1 at the early stage of stem cell differentiation correlated with higher efficacy in generating definitive endoderm and advancing differentiation and maturation of endoderm derivatives. Enforced expression of MIXL1 in the endoderm-inefficient hiPSCs enhanced the propensity of endoderm differentiation, suggesting that modulation of key drivers of lineage differentiation can re-wire hiPSC to the desired lineage propensity to generate the requisite stem cell products.

developmental biology↗

bioRxiv2023

The functional small RNA interactome of vancomycin tolerant Staphylococcus aureus

RNA-RNA interactome profiling techniques have expanded our understanding of sRNA-mRNA interactions in bacteria. However, determining the function of these interactions for hundreds of sRNA-mRNA pairs is a major challenge. At steady-state, protein and mRNA abundances are often highly correlated and lower than expected protein abundance may indicate translational repression of an mRNA. To specifically identify sRNA-mRNA interactions that regulate mRNA translation, we examined the correlation between gene transcript abundance, ribosome occupancy, and protein levels. We used SOMS to cluster genes with similar transcription and translation patterns and identified a cluster of mRNAs that appeared to be post-transcriptionally repressed. By integrating this clustering analysis with sRNA-mRNA interactome data generated in vancomycin tolerant S. aureus by RNase III-CLASH, we identified sRNAs that may be mediating this translational repression. We have confirmed sRNA-dependant post-transcriptional repression of several mRNAs in this cluster. Two of these interactions are mediated by RsaOI, a sRNA that is highly upregulated by vancomycin treatment. While RsaOI is not essential for vancomycin tolerance, we demonstrate regulation of the phosphocarrier protein HPr and the cell-wall autolysin Atl. These findings suggest that RsaOI may serve as a regulator of carbon metabolism and cell wall turnover during cell wall stress exerted by vancomycin.

microbiology↗