library_construction_protocol: All of the organoids were treated with 5um FSK for 3 days before collection. The protocol for nuclei isolation is modified based on 10x Nuclei Isolation from Complex Tissues for Single Cell Multiome ATAC + Gene Expression Sequencing (CG000375). Breifly, the organoids were treated with 0.1% NP40 lysis buffer and homogenized with Dounce tissue grinder (KIMBLE KONTES; 885500-0019) for 5 mins on ice. The suspension was further filtered through a 40 μm cell strainer (pluriSelect) and centrifuged at 500 × g for 5 min at 4 °C. The supernatant was removed. The pellet was washed with wash buffer for three times, then resuspended in pre-cooled nuclei buffer. 10x Chromium Next GEM Single-Cell Multiome ATAC + Gene Expression kit  was used for library preparation according to the instruction 10X single nuclei multiomics kit is suitable to sequencing both ATAC and RNA library from the same cell.