Principal Investigator Harvey Lodish
In collaboration with John Rinn’s group at the Broad Institute, we are examining the roles of large intergenic non-coding RNAs (lincRNAs) in adipogenesis. They profiled the transcriptome of primary adipocytes, pre-adipocytes and cultured adipocytes and identified 481 lincRNAs that are specifically regulated during adipogenesis. Many lincRNAs are adipose-enriched, strongly induced during adipogenesis and bound at their promoters by key adipocyte transcription factors such as PPARɣ and CEBPα. RNAi-mediated loss of function screens identified functional lincRNAs with varying impacts on adipogenesis. They adapted an information-theoretic metric to score cellular phenotypes by quantifying the global “transcriptome shift” between precursor and adipocyte cell states. This analysis honed in on one lincRNA required for proper adipogenesis and that shares numerous copies of a conserved non-coding RNA sequence motif.