Mesoderm

The single-cell transcriptional profile of a human embryo between 16 and 19 days after fertilization reveals parallels and differences in gastrulation in humans as compared with mouse and non-human primate models.

Human pluripotent stem cell aggregates are formed, embedded in Matrigel and directed to differentiate to heart-forming organoids by the chemical WNT pathway modulators CHIR99021 and IWP2.

The BMP antagonist Gremlin1 balances BMP and SHH signalling, endowing limb bud development with robustness. Here, the authors identify enhancers controlling Grem1 levels in an additive, and spatial regulation in a synergistic manner, providing digit patterning with cis-regulatory robustness and evolutionary plasticity.

Nail-patella syndrome (NPS) is characterized by nail dysplasia, absent/hypoplastic patellae, chronic kidney disease, and glaucoma and can be caused by haploinsufficiency of LMX1B; however, not all patients harbor pathogenic LMX1B mutations. Here the authors show that loss-of-function variations in upstream enhancer sequences are responsible for a limb specific form of human NPS.

Human and murine embryonic development has disparities, highlighting the need for primate systems. Here, the authors construct a post-implantation transcriptional atlas from non-human primate embryos and show ISL1 controls a gene regulatory network in the amnion required for mesoderm formation.

Classically, myogenic precursor cells derive from somites, and connective tissues derive from lateral plate mesoderm (LPM). Here the authors identify LPM derived fibroblasts that turn on a myogenic program and fuse to muscle fibers at muscle-tendon junctions, introducing fibroblast transcripts into myofibers.