Departamento de Neurobiología Molecular, Celular y del Desarrollo, Instituto Cajal-CSIC, Avenida Dr. Arce 37, 28002, Madrid, Spain.
Departamento de Bioquímica, Universidade Federal de Sao Paulo UNIFESP, Rua Pedro de Toledo 669, Sao Paulo, 04039032, Brazil.
Biol Res. 2024 Aug 14;57(1):54. doi: 10.1186/s40659-024-00532-y.
Brain damage triggers diverse cellular and molecular events, with astrocytes playing a crucial role in activating local neuroprotective and reparative signaling within damaged neuronal circuits. Here, we investigated reactive astrocytes using a multidimensional approach to categorize their responses into different subtypes based on morphology. This approach utilized the StarTrack lineage tracer, single-cell imaging reconstruction and multivariate data analysis. Our findings identified three profiles of reactive astrocyte responses, categorized by their effects on cell size- and shape- related morphological parameters: "moderate", "strong," and "very strong". We also examined the heterogeneity of astrocyte reactivity, focusing on spatial and clonal distribution. Our research revealed a notable enrichment of protoplasmic and fibrous astrocytes within the "strong" and "very strong" response subtypes. Overall, our study contributes to a better understanding of astrocyte heterogeneity in response to an injury. By characterizing the diverse reactive responses among astrocyte subpopulations, we provide insights that could guide future research aimed at identifying novel therapeutic targets to mitigate brain damage and promote neural repair.
脑损伤引发多种细胞和分子事件，星形胶质细胞在激活受损神经元回路中的局部神经保护和修复信号方面发挥着关键作用。在这里，我们使用多维方法研究反应性星形胶质细胞，根据形态将其反应分类为不同的亚型。该方法利用 StarTrack 谱系示踪剂、单细胞成像重建和多变量数据分析。我们的研究结果确定了三种反应性星形胶质细胞反应的特征，根据其对细胞大小和形状相关形态参数的影响进行分类：“中度”、“强烈”和“非常强烈”。我们还研究了星形胶质细胞反应的异质性，重点关注空间和克隆分布。我们的研究表明，在“强烈”和“非常强烈”反应亚型中，原浆型和纤维型星形胶质细胞明显富集。总的来说，我们的研究有助于更好地理解星形胶质细胞对损伤的异质性反应。通过描述星形胶质细胞亚群中不同的反应性反应，我们提供了可以指导未来研究的见解，以确定新的治疗靶点来减轻脑损伤并促进神经修复。
