Endogenous FGF gradients are required for cell fate patterning in 2D human gastruloids

The role of FGF is the least understood of the morphogens driving mammalian gastrulation. Here we investigated the function of FGF in a stem cell model for human gastrulation known as a 2D gastruloid. We found a ring of FGF-dependent ERK activity closely follows the emergence of primitive streak (PS)-like cells but expands further inward. We showed that this ERK activity pattern is required for PS-like differentiation and depends on localized activation of basally polarized FGF receptors (FGFR) by endogenous FGF gradients. By single cell RNA-sequencing, we identified the main receptor to be FGFR1 and the key ligands FGF2/4/17 and showed that this is similar to the human and monkey embryo but different from the mouse. Overall design: Micropatterned human pluripotent stem cells (hPSCs) were collected at 42 hours after treatment with BMP4 for single cell RNA sequencing with 10X Genomics Chromium Controller. GSE271604_42h_rep1_filtered_Counts.csv.gz is reanalyzed data for GEO sample GSM5517031 (Series GSE182057).