In Client successes

New publication success!

A collaborative team of researchers based at the Shanghai Institute of Immunology, the First affiliated hospital of Zhejiang University, the Singapore Immunology Network, the National University of Singapore (NUS), and the SingHealth Duke-NUS Academic Medical Center, have published the results of a superb study into how mutations in CSF-1R affect microglia to promote neurodegenerative disease.

The focus of this study was hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) – a rare yet fatal neurodegenerative disease underpinned by mutations in CSF-IR. Wei Jie Wong and colleagues developed a state-of-the-art macrophage and forebrain organoid co-culture derived from induced pluripotent stem cells isolated from two patients with HDLS.

Compared to control organoids (in which CSF-1R gene mutations were corrected), they found that the patient-derived macrophages exhibited a metabolic shift towards the glycolytic pathway and reduced CSF-1 sensitivity. The result of this shift was an increase in IL-1β production and an activated inflammatory phenotype. RNA sequencing revealed that these macrophages existed in a reactive state, which led to impaired neuronal cell regulation.

This ground breaking study has provided yet more evidence of the diverse roles of microglia, as well as great insight into the pathological mechanisms of HDLS. We have no doubt that immunologists, neuroscientists, and clinicians will all be thrilled to read this exciting study and learn how Wei Jie Wong et al. tackled this complex question.

If you are interested to learn more, the paper is now available to download here, complete with referee reports:

Many congratulations to the whole team: Wei Jie Wong, Yi Wen Zhu, Hai Ting Wang, Jia Wen Qian, Ziyi Li, Li Song, Zhao Yuan Liu, Wei Guo, Shuang Yan Zhang, Bing Su, Fang Ping He, Kang Wang and Florent Ginhoux!