library_construction_protocol: The single-cell isolation procedures were performed according to the protocol previously described (Ma et al., 2019a). In brief, the pIVC cynomolgus embryos were  dissected by removing the extraembryonic tissues, then the inner embryonic bodies were digested with 500 μL of 1 × TrypLE for 15 min at 37°C and dissociated into single cells by mouth pipetting. Advanced DMEM/F12 containing 10% FBS was added to terminate the enzymatic reaction and the cells were centrifuged at 300 g for 5 min at room temperature, followed by the resuspension with 100 μL pre-cold 0.1% BSA/PBS. Single cells were individually picked into ice-cold lysis buffer under stereoscopic microscope. single cells were picked of each stage and then the subjected to construct scChaRM-seq library. The method of library construction was described in our recently published method (Yan et al., 2021). In brief, in vitro CpG methylation was performed by M.CviPI (New England Biolabs, NEB) supplemented with S-adenosyl-methionine (SAM;NEB) and terminated by adding RLT buffer (QIAGEN). Then the genome DNA and mRNA were separated by capturing mRNA with oligo(dT) primers conjugated beads (Invitrogen), the supernatant containing genomic DNA was transferred into another PCR tube to bisulfite conversion (Zymo Research) and DNA library construction using previously descried TAILS method (Gu et al., 2019). The captured mRNA was subjected correspondingly to cDNA synthesis, PCR amplification and library construction (Gu et al., 2019).