RESUMEN
Understanding the cellular and molecular determinants of mammalian tissue regeneration and repair is crucial for developing effective therapies that restore tissue architecture and function. In this review, we focus on the cell types involved in scarless wound response and regeneration of spiny mice (Acomys). Comparative -omics approaches with scar-prone mammals have revealed species-specific peculiarities in cellular behavior during the divergent healing trajectories. We discuss the developing views on which cell types engage in restoring the architecture of spiny mouse tissues through a co-ordinated spatiotemporal response to injury. While yet at the beginning of understanding how cells interact in these fascinating animals to regenerate tissues, spiny mice hold great promise for scar prevention and anti-fibrotic treatments.
Asunto(s)
Regeneración , Cicatrización de Heridas , Animales , Regeneración/fisiología , Cicatrización de Heridas/genética , Cicatriz/patología , Murinae , Mamíferos , RatonesRESUMEN
In contrast to other mammals, the spiny mouse (Acomys) regenerates skin and ear tissue, which includes hair follicles, glands, and cartilage, in a scar-free manner. Ear punch regeneration is asymmetric with only the proximal wound side participating in regeneration. Here, we show that cues originating from the proximal side are required for normal regeneration and use spatially resolved transcriptomics (tomo-seq) to understand the molecular and cellular events underlying this process. Analyzing gene expression across the ear and comparing expression modules between proximal and distal wound sides, we identify asymmetric gene expression patterns and pinpoint regenerative processes in space and time. Moreover, using a comparative approach with nonregenerative rodents (Mus, Meriones), we strengthen a hypothesis in which particularities in the injury-induced immune response may be one of the crucial determinants for why spiny mice regenerate whereas their relatives do not. Our data are available in SpinyMine, an easy-to-use and expandable web-based tool for exploring Acomys regeneration-associated gene expression.
Asunto(s)
Murinae , Cicatrización de Heridas , Animales , Cicatrización de Heridas/genética , Murinae/genética , Transcriptoma , Regeneración/genética , Piel , Mamíferos/genéticaRESUMEN
During development cells become restricted in their differentiation potential by repressing alternative cell fates, and the Polycomb complex plays a crucial role in this process. However, how alternative fate genes are lineage-specifically silenced is unclear. We studied Ultrabithorax (Ubx), a multi-lineage transcription factor of the Hox class, in two tissue lineages using sorted nuclei and interfered with Ubx in mesodermal cells. We find that depletion of Ubx leads to the de-repression of genes normally expressed in other lineages. Ubx silences expression of alternative fate genes by retaining the Polycomb Group protein Pleiohomeotic at Ubx targeted genomic regions, thereby stabilizing repressive chromatin marks in a lineage-dependent manner. Our study demonstrates that Ubx stabilizes lineage choice by suppressing the multipotency encoded in the genome via its interaction with Pho. This mechanism may explain why the Hox code is maintained throughout the lifecycle, since it could set a block to transdifferentiation in adult cells.