LncRNA SNHG26 facilitates inflammatory to proliferative state transition of keratinocyte progenitors during wound healing

The epidermal stem cell transition from inflammation to proliferation is a crucial process in tissue repair. However, the molecular mechanism underlying this process is poorly understood. Combined with lncRNA expression profiling of human acute wounds and functional screening, we identified SNHG26 as a pivotal regulator of inflammatory to proliferative state transition of keratinocyte progenitor cells. Snhg26-deficient mice showed impaired wound healing characterized by increased inflammatory response and decreased reepithelization in the wound. Consistently, single-cell transcriptomic analysis of the wound-edge tissue identified proliferative, migratory, and proinflammatory basal progenitors, which were dramatically changed in Snhg26 deficient mice. Mechanically, SNHG26 binds with ILF2 to relocate this transcription factor from the inflammatory gene loci (such as JUN) to the LAMB3 genomic loci. Collectively, this work identified a conserved lncRNA SNHG26 as a master regulator of epidermal stem cell state transition from inflammation to proliferation, highlighting the importance of lncRNAs in tissue repair and regeneration. Overall design: The epidermal stem cell transition from inflammation to proliferation is a crucial process in tissue repair. However, the molecular mechanism underlying this process is poorly understood. We identified SNHG26 as a pivotal regulator of inflammatory to proliferative state transition of keratinocyte progenitor cells. The Snhg26-deficient mice showed impaired wound healing. We collected mice skin and acute wound edge (Day3) samples and performed 10x single cell sequencing according to the manufacture instruction. Mechanically, SNHG26 binds with ILF2. To study the effect of silencing of SNHG26 on ILF2 interaction with genome, we knockdown SNHG26 followed by TNFa stimulation. Then we performed ILF2 CHIP sequencing. To study which genomic loci the SNHG26 interact with, we performed SNHG26 ChIRP assay by using antisense oligoes targeting SNHG26. The chromatin associated with SNHG26 antisense oligoes was purified and subjected to deep DNA sequencing.