Fig. 6

Snapshot and temporal scRNA-seq profiling on progenitor cell states. scRNA-seq from snapshots of lineage-specific progenitors revealed that hypoxia enhances DE differentiation in a time-sensitive manner, likely acting on the mesendodermal progenitors. The differentiation trajectory was reconstructed by Wave-Crest (blue arrow) using time course scRNA-seq along the differentiation towards DE cells. Results from loss-of-function and gain-of-function experiments demonstrated that KLF8 function as a positive regulator mediating cell states transitions from T ⁺ mesendoderm to CXCR4 ⁺ DE cells. We hypothesize that KLF8 can suppress T ⁺ state and in turn enhance the activation of CXCR4 ⁺ state. The molecular mechanisms of how KLF8 directly or indirectly suppress T ⁺ state require future investigation