Mammary organoids were collected after 8 days of doxycycline induction and lysed for RNA purification using a commercial total RNA Purification kit (Favorgen, Cat# FATRK 011-2). mRNA was purified using poly-T oligo-attached magnetic beads and fragmented randomly by addition of fragmentation buffer. First strand cDNA was synthesized using random hexamer primers and M-MuLV Reverse Transcriptase (RNase H-). Second strand cDNA synthesis was subsequently performed using DNA Polymerase I and RNase H. Double-stranded cDNA was purified using AMPure XP beads. Remaining overhangs of the purified double-stranded cDNA were converted into blunt ends via exonuclease/polymerase activities. After adenylation of 3' ends of DNA fragments, NEBNext Adaptor with hairpin loop structure was ligated to prepare for hybridization. In order to select cDNA fragments of preferentially 150~200 bp in length, the library fragments were purified with AMPure XP system (Beckman Coulter, Beverly, USA).  The final library was prepared by PCR amplification and purification of PCR products using AMPure XP beads.