Unexpected contribution of fibroblasts to the muscle lineage during foetal myogenesis and role of BMP signalling in this process

ABSTRACT: Purpose : Positional information driving limb muscle patterning is considered to be contained in lateral plate mesoderm-derived tissues, such as tendon or muscle connective tissue and not in myogenic cells themselves. The current consensus is that myogenic cells originate from somites, while connective tissue fibroblasts originate from the lateral plate mesoderm. We challenged this model by cell and genetic lineage tracing experiments and identified that a subpopulation of limb myogenic cells did not originate from somite or Pax3 lineage, but rather originated from the lateral plate mesoderm and were derived from Osr1 and Scx lineages. Results: Analysis of single-cell RNA-sequencing data obtained from limb cells at successive developmental stages identified a subpopulation of cells displaying a dual muscle and connective tissue signature, in addition to independent muscle and connective tissue populations. Active BMP signalling was detected in this junctional cell sub-population and at the tendon/muscle interface in developing limbs. BMP gain- and loss-of-function experiments performed in vivo and in vitro showed that this signalling pathway regulated a fibroblast-to-myoblast conversion. Conclusions: We propose that localised BMP signalling converts a subset of lateral plate mesoderm-derived fibroblasts to a myogenic fate and establishes a boundary of fibroblast-derived myonuclei at the tendon/muscle interface to control the muscle pattern during limb development and myotendinous formation.

ORGANISM(S): Gallus gallus

PROVIDER: GSE166981 | GEO | 2021/05/06

REPOSITORIES: GEO