PRIMATE/HUMAN-SPECIFIC FEATURES AND FUNCTION OF TROPHOBLAST LINEAGE

Abstract

UNDERSTANDING THE UNDERLYING MOLECULAR EVENTS IN THE PRIMATE EVOLUTION HAS BEEN A MAJOR CHALLENGE FOR ADDRESSING THE CAUSE OF HUMAN EMBRYO IMPLANTATION DISORDERS AND INFERTILITY PROBLEMS. TO ADDRESS THIS, AN IN VITRO SYSTEM HAS BEEN DEVELOPED WITH THE USE OF HUMAN EMBRYONIC STEM CELLS DIFFERENTIATED TOWARDS THE SYNCYTIOTROPHOBLAST LINEAGE. I ARGUE THIS MODEL RECAPITULATES THE FORMATION OF THE PRIMITIVE SYNCYTIUM. BY APPLYING HIGH THROUGHPUT SEQUENCING METHODS, WE FOUND WITHIN THE HUMAN SYNCYTIOTROPHOBLAST PROTEIN CODING TRANSCRIPTOME; PRIMATE-SPECIFIC FEATURES RESULTED FROM RECENT GENE DUPLICATIONS, POSITIVE SELECTION AND CO-OPTION OF ENDOGENOUS RETROVIRAL GENES. EXTENSIVE NOVEL REGULATORY CHANGE ALTERING GENE EXPRESSION WAS IDENTIFIED. THESE CIS-REGULATORY NOVELTIES AROSE BOTH THROUGH APPARENT ACCUMULATION OF SINGLE NUCLEOTIDE MUTATION AND THE CO-OPTION OF ERV LONG TERMINAL REPEATS (LTRS). THESE RESULTS PROVIDE A MECHANISTIC INSIGHT IN THE EVOLUTIONARY EVENTS, WHICH IS INVOLVED IN THE