Pluto Bioinformatics

GSE44875: Transcriptome profiling of human pancreatic lineage specification using RNA-seq

Bulk RNA sequencing

Differentiation of functional pancreatic beta cells from human pluripotent stem cells provide a promising source for cell therapy, and should also facilitate human pancreas developmental study. To achieve robust yield of functional human beta cells, comprehensive understanding on the dynamic gene expression pattern and regulation is emergently required and novel regulators are expected to guide beta cell differentiation. Here we perform RNA-seq based transcriptome profiling using undifferentiated human ESCs, and purified ESC-derivate (definitive endoderm, pancreatic progenitors) as well as sorted human primary alpha cells, beta cells and exocrine cells. First, the protein-coding gene expression dynamics reveals the in vitro differentiation indeed mimics the in vivo development as expected. Genomically, the total number of active transcribed genes at respective developmental stage goes down over pancreatic lineage differentiation progression. Biologically, a screening of several TGF-beta signaling related chemicals based on the sequencing information leads us to identify a potent chemical greatly improving pancreatic differentiation. In the other hand, we identify hundreds of long non-coding RNAs (lncRNAs) which dynamically expresses over pancreatic lineage differentiation. Bioinformatics analysis further shows lncRNAs are more stage-specific than protein-coding genes. We also identify alpha and beta cell specific lncRNAs and some located in genomic loci underlying diabetes susceptibility. In summary, we have presented comprehensive genome-wide transcriptional dataset over beta cell lineage and identified hundreds of dynamically expressed lncRNAs. These valuable data should shed light on the studies on human pancreas development and beta cell differentiation. SOURCE: Yuting Liu (Yuting.Liu@childrens.harvard.edu) - Yi Zhang lab Harvard Medical School