YTHDF1-regulated expression of TEAD1 contributes to the maintenance of intestinal stem cells.

N6-methyladenosine (mA) mRNA modification has been defined as a crucial regulator in various biological processes. Recent studies indicated an essential role of YTHDF1, an mA reader, in the maintenance of intestinal stem cells (ISCs), while the detailed mechanism remains to be explored. By searching our mA sequencing, RNA sequencing, and ribosome profiling data, we identified the transcriptional enhanced associate domain 1 (TEAD1) as a direct target of YTHDF1. We confirmed the presence of mA modifications in TEAD1 mRNA and its binding with YTHDF1. Knockdown of either mA methyltransferase METTL3 or YTHDF1 reduced the translation of TEAD1. TEAD1 was highly expressed in ISCs, while depletion of TEAD1 inhibited proliferation and induced differentiation of organoids. Overexpression of TEAD1 reversed the impaired stemness elicited by YTHDF1 depletion. These findings identify TEAD1 as a functional target of mA-YTHDF1 in sustaining intestinal stemness.