This study investigates the role of vitamin A in regulating lineage plasticity, a critical process for stem cells to transition between different cell fates. The authors found that retinoic acid (atRA) is a key regulator of this process, particularly in skin stem cells. By screening small molecules, they identified atRA as a potent regulator of lineage plasticity in hair follicle stem cells (HFSCs). AtRA was shown to reduce the expression of KLF5, a marker of lineage plasticity, and promote the expression of SOX9, a marker of HFSC identity. The study also revealed that atRA acts at the chromatin level to regulate gene expression, specifically targeting master regulators of stem cell identity. Furthermore, atRA was found to function in concert with other signaling pathways, such as BMPs and WNTs, to maintain HFSC identity and regulate lineage progression. The findings highlight the importance of resolving lineage plasticity for proper tissue regeneration and provide insights into the therapeutic potential of atRA in treating conditions like chronic wounds and cancers.This study investigates the role of vitamin A in regulating lineage plasticity, a critical process for stem cells to transition between different cell fates. The authors found that retinoic acid (atRA) is a key regulator of this process, particularly in skin stem cells. By screening small molecules, they identified atRA as a potent regulator of lineage plasticity in hair follicle stem cells (HFSCs). AtRA was shown to reduce the expression of KLF5, a marker of lineage plasticity, and promote the expression of SOX9, a marker of HFSC identity. The study also revealed that atRA acts at the chromatin level to regulate gene expression, specifically targeting master regulators of stem cell identity. Furthermore, atRA was found to function in concert with other signaling pathways, such as BMPs and WNTs, to maintain HFSC identity and regulate lineage progression. The findings highlight the importance of resolving lineage plasticity for proper tissue regeneration and provide insights into the therapeutic potential of atRA in treating conditions like chronic wounds and cancers.