Vitamin A resolves lineage plasticity to orchestrate stem cell lineage choices. A study published in Science reveals that retinoic acid (atRA) is critical for resolving lineage plasticity in skin stem cells, enabling them to regenerate hair and repair wounds. The research shows that atRA is produced locally in hair follicle stem cell niches and regulates the identity and function of these cells. By resolving lineage plasticity, atRA helps maintain the stem cell identity and supports tissue regeneration. The study used a combination of high-throughput screening, cell culture, and in vivo mouse genetics to identify atRA as a key regulator of stem cell fate decisions. The findings have therapeutic implications for hair growth, chronic wounds, and cancers where lineage plasticity is unresolved. The study also highlights the importance of atRA in regulating the balance between hair follicle stem cells and epidermal stem cells during tissue repair. The research demonstrates that atRA acts at the level of nuclear retinoid receptors to directly resolve lineage plasticity and maintain stem cell identity. The study further shows that atRA functions with BMPs and WNTs to regulate hair follicle stem cell identity and lineage progression. The findings underscore the importance of resolving lineage plasticity for proper tissue regeneration and highlight the role of atRA in maintaining stem cell function during wound repair. The study provides insights into the complex signaling networks that govern stem cell behavior and has implications for the development of therapeutic strategies for skin and hair disorders.Vitamin A resolves lineage plasticity to orchestrate stem cell lineage choices. A study published in Science reveals that retinoic acid (atRA) is critical for resolving lineage plasticity in skin stem cells, enabling them to regenerate hair and repair wounds. The research shows that atRA is produced locally in hair follicle stem cell niches and regulates the identity and function of these cells. By resolving lineage plasticity, atRA helps maintain the stem cell identity and supports tissue regeneration. The study used a combination of high-throughput screening, cell culture, and in vivo mouse genetics to identify atRA as a key regulator of stem cell fate decisions. The findings have therapeutic implications for hair growth, chronic wounds, and cancers where lineage plasticity is unresolved. The study also highlights the importance of atRA in regulating the balance between hair follicle stem cells and epidermal stem cells during tissue repair. The research demonstrates that atRA acts at the level of nuclear retinoid receptors to directly resolve lineage plasticity and maintain stem cell identity. The study further shows that atRA functions with BMPs and WNTs to regulate hair follicle stem cell identity and lineage progression. The findings underscore the importance of resolving lineage plasticity for proper tissue regeneration and highlight the role of atRA in maintaining stem cell function during wound repair. The study provides insights into the complex signaling networks that govern stem cell behavior and has implications for the development of therapeutic strategies for skin and hair disorders.