Yabaji Shivraj M, Rukhlenko Oleksii S, Chatterjee Sujoy, Bhattacharya Bidisha, Wood Emily, Kasaikina Marina, Kholodenko Boris, Gimelbrant Alexander A, Kramnik Igor
The National Emerging Infectious Diseases Laboratories (NEIDL), Boston University.
Systems Biology Ireland, School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland.
bioRxiv. 2023 Feb 10:2023.02.09.527908. doi: 10.1101/2023.02.09.527908.
Understanding cell state transitions and purposefully controlling them to improve therapies is a longstanding challenge in biological research and medicine. Here, we identify a transcriptional signature that distinguishes activated macrophages from TB-susceptible and TB-resistant mice. We then apply the cSTAR (cell State Transition Assessment and Regulation) approach to data from screening-by-RNA sequencing to identify chemical perturbations that shift the. transcriptional state of the TB-susceptible macrophages towards that of TB-resistant cells. Finally, we demonstrate that the compounds identified with this approach enhance resistance of the TB-susceptible mouse macrophages to virulent .
理解细胞状态转变并有意控制它们以改善治疗方法是生物学研究和医学中一项长期存在的挑战。在这里，我们鉴定出一种转录特征，可区分活化的巨噬细胞与对结核病易感和耐药的小鼠。然后，我们将cSTAR（细胞状态转变评估与调控）方法应用于RNA测序筛选的数据，以识别能将结核病易感巨噬细胞的转录状态转变为耐药细胞转录状态的化学扰动。最后，我们证明用这种方法鉴定出的化合物可增强结核病易感小鼠巨噬细胞对强毒……的抗性。
