Individual cells were directly sorted into 96-well plates containing methyltransferase reaction mixture and incubated for 30 minutes at 37°C. Dynabeads Myone Carboxylic Acid (Invitrogen, 65011) was used to capture nuclei, which were used to carry out scBisulfite-seq to profile DNA methylation and chromatin accessibility. Bisulfite-converted DNA was amplified with biotinylated random primer and klenow exo– polymerase (NEB, M0212L) for 7 rounds and excess primer was removed by exonuclease I (NEB, M0293L). After second strand synthesis, the library was amplified by KAPA HiFi HotStart ReadyMix (Kapa Biosystems, KK2602) for 14 cycles.