Duchenne muscular dystrophy (DMD) physiopathology is still not fully understood and a prenatal onset is suspected but difficult to address. Bone morphogenetic protein 4 (BMP4) is a critical signaling molecule involved in mesoderm commitment. Human induced pluripotent stem cells (hiPSCs) from DMD and healthy individuals and human embryonic stem cells (hESCs) treated with BMP4 were used to model the early steps of myogenesis in normal and DMD contexts. Unexpectedly, 72h following BMP4 treatment, a new long DMD transcript was detected in all tested hiPSCs and hESCs, at levels similar to that found in adult skeletal muscle. This novel transcript named “Dp412e” has a specific untranslated first exon which is conserved only in a sub-group of anthropoids including human. Deciphering the regulation process(es) and the function(s) associated to this new dystrophin isoform can contribute to a better understanding of DMD physiopathology and potential developmental defects.
