Institute of Molecular Medicine, Ulm University, Ulm, Germany.
Terry Fox Laboratory, BC Cancer Research Centre, Vancouver, BC, Canada.
Nat Commun. 2024 Nov 26;15(1):10250. doi: 10.1038/s41467-024-54638-8.
The distribution of biomolecules within cells changes upon aging and diseases. To quantitatively determine the spatial distribution of components inside cells, we built the user-friendly open-source 3D-cell-image analysis platform Cell Detection and Analysis of Intensity Lounge (CellDetail). The algorithm within CellDetail is based on the concept of the dipole moment. CellDetail provides quantitative values for the distribution of the polarity proteins Cdc42 and Tubulin in young and aged hematopoietic stem cells (HSCs). Septin proteins form networks within cells that are critical for cell compartmentalization. We uncover a reduced level of organization of the Septin network within aged HSCs and within senescent human fibroblasts. Changes in the Septin network structure might therefore be a common feature of aging. The level of organization of the network of Septin proteins in aged HSCs can be restored to a youthful level by pharmacological attenuation of the activity of the small RhoGTPase Cdc42.
细胞内生物分子的分布会随着衰老和疾病而改变。为了定量确定细胞内成分的空间分布,我们构建了用户友好的开源 3D 细胞图像分析平台——细胞检测和强度分析休息室(CellDetail)。CellDetail 中的算法基于偶极矩的概念。CellDetail 为年轻和衰老的造血干细胞(HSCs)中极性蛋白 Cdc42 和微管蛋白的分布提供了定量值。 septin 蛋白在细胞内形成网络,对细胞区室化至关重要。我们发现衰老的 HSCs 和衰老的人成纤维细胞中 septin 网络的组织水平降低。因此,septin 网络结构的变化可能是衰老的一个共同特征。通过药理学抑制小 RhoGTPase Cdc42 的活性,可将衰老 HSCs 中 septin 蛋白网络的组织水平恢复到年轻水平。