The present invention provides new and improved methods for performing in situ transcriptomics from rare "cells of interest" present in complex multicellular environments.These methods involve expressing a recombinant cytosine deaminase enzyme in the cells of interest, and also supplying an exogenous non-naturally occurring halogenated cytosine substrate for the enzyme - which results in the generation halogenated uridine which is incorporated into RNA, thereby "tagging" RNA in the cells of interest. The invention also provides several variations of such methods that significantly improve the sensitivity and specificity of the RNA labeling. Furthermore, the invention also provides simple and efficient methods for purifying the tagged RNA. The purified tagged RNA can be used to analyze the transcriptomes of the cells of interest by RNA-sequencing and other methods.
