UMMS Affiliation

Program in Bioinformatics and Integrative Biology; Program in Molecular Medicine; Garber Lab

Publication Date


Document Type



Bioinformatics | Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Genetics and Genomics | Molecular Biology | Nervous System Diseases | Neuroscience and Neurobiology


Despite advances in understanding the pathophysiology of Fragile X syndrome (FXS), its molecular basis is still poorly understood. Whole brain tissue expression profiles have proved surprisingly uninformative, therefore we applied single cell RNA sequencing to profile an FMRP deficient mouse model with higher resolution. We found that the absence of FMRP results in highly cell type specific gene expression changes that are strongest among specific neuronal types, where FMRP-bound mRNAs were prominently downregulated. Metabolic pathways including translation and respiration are significantly upregulated across most cell types with the notable exception of excitatory neurons. These effects point to a potential difference in the activity of mTOR pathways, and together with other dysregulated pathways, suggest an excitatory-inhibitory imbalance in the Fmr1-knock out cortex that is exacerbated by astrocytes. Our data demonstrate that FMRP loss affects abundance of key cellular communication genes that potentially affect neuronal synapses and provide a resource for interrogating the biological basis of this disorder.


Neurons, Gene expression, Astrocytes, Messenger RNA, Mouse models, Protein translation, Mitochondria, Synapses

Rights and Permissions

Copyright: © 2022 Donnard et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

DOI of Published Version



Donnard E, Shu H, Garber M. Single cell transcriptomics reveals dysregulated cellular and molecular networks in a fragile X syndrome model. PLoS Genet. 2022 Jun 8;18(6):e1010221. doi: 10.1371/journal.pgen.1010221. PMID: 35675353; PMCID: PMC9212148. Link to article on publisher's site

Journal/Book/Conference Title

PLoS genetics


This article is based on a previously available preprint in bioRxiv.

Related Resources

Link to Article in PubMed

PubMed ID


Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.