Abstract:
Single-cell technologies have recently expanded the possibilities for researchers to gain, at an unprecedented resolution level, knowledge about tissue composition, cell complexity, and heterogeneity. Moreover, the integration of data coming from different technologies and sources also offers, for the first time, the possibility to draw a holistic portrait of how cells behave to sustain tissue physiology during the human lifespan and disease. Here, we interrogated and integrated publicly available single-cell RNAseq data to advance the understanding of how macrophages, fibro/adipogenic progenitors, and other cell types establish gene regulatory networks and communicate with each other in the muscle tissue. We identified altered gene signatures and signaling pathways associated with the dystrophic condition, including an enhanced Spp1-Cd44 signaling in dystrophic macrophages. We shed light on the differences among dystrophic muscle aging, considering wild type, mdx, and more severe conditions as in the case of the mdx-2d model. Contextually, we provided details on existing communication relations between muscle niche cell populations, highlighting increased interactions and distinct signaling events that these cells stablish in the dystrophic microenvironment. We believe our findings can help scientists to formulate and test new hypotheses by moving towards a more complete understanding of muscle regeneration and immune system biology.
摘要:
单细胞技术最近扩大了研究人员获得的可能性,以前所未有的分辨率,有关组织组成的知识,细胞复杂性,和异质性。此外,来自不同技术和来源的数据的整合也提供了,第一次,在人类寿命和疾病期间,绘制细胞如何维持组织生理的整体肖像的可能性。这里,我们询问并整合了公开可用的单细胞RNAseq数据,以促进对巨噬细胞,纤维/脂肪原祖细胞,和其他细胞类型建立基因调控网络,并在肌肉组织中相互交流。我们确定了与营养不良状况相关的基因特征和信号通路的改变,包括在营养不良的巨噬细胞中增强的Spp1-Cd44信号传导。我们揭示了营养不良性肌肉衰老之间的差异,考虑到野生型,mdx,和更严格的条件,如MDX-2d模型。上下文中,我们提供了肌肉小生境细胞群之间现有交流关系的细节,强调这些细胞在营养不良微环境中稳定的相互作用增加和不同的信号事件。我们相信我们的发现可以帮助科学家通过对肌肉再生和免疫系统生物学的更完整的理解来制定和测试新的假设。