The role of the gene Mest during mouse digit tip regeneration

The distal mouse digit tip undergoes complex tissue regeneration following amputation, a process facilitated by the formation of a cellular structure called the blastema. Through single-cell RNA sequencing of the blastema, we identified the gene Mest (mesoderm specific transcript) highly expressed in a subset of blastemal fibroblasts. To determine if Mest expression is necessary for mouse digit tip regeneration, we analyzed Mest wildtype (WT) versus homozygous knockout (KO) post amputation digits. Through single-cell sequencing and FACS analysis of WT and KO regenerating tissues, we determined that this phenomenon was due to a prolonged immune response in the KO digits. Overall design: Cohorts of adult Mest genetic knock-out (KO) mice and Mest wild-type (WT) mice underwent digit tip amputation; 12 days post-amputation, digit tip blastemas were collected and used for single cell RNA sequencing and analysis.