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Uncovering the Genetic Profiles Underlying the Intrinsic Organization of the Human Cerebellum

By Yaping Wang, Lin Chai, Deying Li, Chaohong Gao, Congying Chu, Zhengyi Yang, Yu Zhang, Junhai Xu, Jens Randel Nyengaard, Simon B. Eickhoff, Bing Liu, Kristoffer Hougaard Madsen, Tianzi Jiang, Lingzhong Fan

Posted 24 Jun 2021
bioRxiv DOI: 10.1101/2021.06.23.448673

The functional diversity of the human cerebellum is hypothesized to be derived more from its extensive connections rather than being limited to its mostly invariant architecture. However, whether and how the hypothesized determination of cerebellar connections in its intrinsic organization interact with microscale gene expression is still unknown. Here we decode the genetic profiles of the cerebellar functional organization by investigating the genetic substrates simultaneously linking cerebellar functional heterogeneity and its drivers, i.e., the connections. We not only identified 443 network-specific genes but also discovered that their co-expression pattern correlated strongly with intra-cerebellar connectivity. Of these genes, 90 were also linked to the cortico-cerebellar cognitive-limbic networks. Then, using a "virtual gene knock-out" analysis, two gene sets involved in different biological processes and diseases were distinguished. Collectively, our results could help to rethink the genetic substrates underlying the cerebellar functional organization, as well as offer possible interpretability for its engagement in neuropsychiatric disorders.

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