Loubet-Senear Kaitlyn, Srivastava Mansi
bioRxiv. 2024 Jul 4:2024.07.04.601589. doi: 10.1101/2024.07.04.601589.
The wide distribution of regenerative capacity across the animal tree of life raises the question of how regeneration has evolved in distantly-related animals. Given that whole-body regeneration shares the same end-point - formation of a functional body plan - as embryonic development, it has been proposed that regeneration likely recapitulates developmental processes to some extent. Therefore, understanding how developmental processes are reactivated during regeneration is important for uncovering the evolutionary history of regeneration. Comparative transcriptomic studies in some species have revealed shared gene expression between development and regeneration, but it is not known whether these shared expression profiles correspond to shared functions, and which mechanisms activate expression of developmental genes during regeneration. We sought to address these questions using the acoel , which is amenable to studies of both embryonic development and whole-body regeneration. By examining functionally validated regeneration processes during development at single-cell resolution, we found that whereas patterning and cellular differentiation are largely similar, wound response programs have distinct dynamics between development and regeneration. Chromatin accessibility analyses revealed that regardless of playing concordant or divergent roles during regeneration and development, genes expressed in both processes are frequently controlled by the same regulatory regions, potentially via utilization of distinct transcription factor binding sites. This study extends the known correspondence of development and regeneration from broad transcriptomic similarity to include patterning and differentiation processes. Further, our work provides a catalog of regulatory regions and binding sites that potentially regulate developmental genes during regeneration, fueling comparative studies of regeneration.
再生能力在动物生命之树上广泛分布,这引发了一个问题:再生在亲缘关系较远的动物中是如何进化的。鉴于全身再生与胚胎发育有着相同的终点——形成一个功能完整的身体结构,有人提出再生可能在一定程度上重演了发育过程。因此,了解发育过程在再生过程中是如何重新激活的,对于揭示再生的进化历史至关重要。一些物种的比较转录组学研究揭示了发育和再生之间共享的基因表达,但尚不清楚这些共享的表达谱是否对应着共享的功能,以及在再生过程中是哪些机制激活了发育基因的表达。我们试图利用扁形虫来解决这些问题,扁形虫适合进行胚胎发育和全身再生的研究。通过在单细胞分辨率下研究发育过程中经过功能验证的再生过程,我们发现,虽然模式形成和细胞分化在很大程度上相似,但伤口反应程序在发育和再生之间具有不同的动态变化。染色质可及性分析表明,无论在再生和发育过程中发挥一致还是不同的作用,在这两个过程中表达的基因通常都受相同调控区域的控制,可能是通过利用不同的转录因子结合位点。这项研究将发育和再生之间已知的对应关系从广泛的转录组相似性扩展到包括模式形成和分化过程。此外,我们的工作提供了一份可能在再生过程中调控发育基因的调控区域和结合位点目录,为再生的比较研究提供了助力。