Cell state transition analysis identifies interventions that improve control of M. tuberculosis infection by susceptible macrophages

Yabaji, S. M.; Rukhlenko, O. S.; Chatterjee, S.; Bhattacharya, B.; Wood, E.; Kasaikina, M.; Kholodenko, B.; Gimelbrant, A. A.; Kramnik, I.

doi:10.1101/2023.02.09.527908

bioRxiv · 10.1101/2023.02.09.527908

Cell state transition analysis identifies interventions that improve control of M. tuberculosis infection by susceptible macrophages

Yabaji, S. M.·Rukhlenko, O. S.·Chatterjee, S.·Bhattacharya, B.·Wood, E.·Kasaikina, M.·Kholodenko, B.·Gimelbrant, A. A.·Kramnik, I.

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Abstract

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 M. tuberculosis.

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Yabaji, S. M., Rukhlenko, O. S., Chatterjee, S., Bhattacharya, B., Wood, E., Kasaikina, M., Kholodenko, B., Gimelbrant, A. A., Kramnik, I.. 2023-02-10. Cell state transition analysis identifies interventions that improve control of M. tuberculosis infection by susceptible macrophages. https://doi.org/10.1101/2023.02.09.527908

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