The Doctor of Philosophy Seminar and Examination of Xiaoran Wei

Biography

Xiaoran Wei is a PhD candidate in Biomedical and Veterinary Sciences. She graduated from Beijing Jiaotong University with bachelor’s degree in bioinformatics in 2018 and came to Virginia Tech for her PhD at the same year. Her research interests include astrocyte development, epigenetics and bioinformatics.

Funded by

National Institutes of Health
Virginia Tech Alliance for Neurodevelopment Research
Virginia-Maryland College of Veterinary Medicine Office of Research and Graduate Studies

Awards and Academic Achievements

·       Neurodevelopment Research seed funding, Virginia tech, Spring 2023
·       GPSS travel funding, Virginia tech, 2023

Lay Language Abstract 

Astrocytes are an abundant brain cell type that play crucial roles in maintaining brain health and supporting neuron functions. Astrocytes develop right after birth and reach full maturity by the second month in rodents. Throughout life, astrocytes play crucial roles in stabilizing the brain's environment and supporting most brain functions. the formation of astrocyte complex morphology is regulated by brain-derived neurotrophic factor (Bdnf), which interacts with a specific receptor called TrkB.T1 found mainly in astrocytes. Another form of this receptor, TrkB.FL, is primarily found in neurons. Despite the importance of TrkB.T1 in astrocyte development and function, the reason for high expression and role in astrocytes were not well understood. Previous studies in human postmortem samples indicated that DNA methylation level of the gene NTRK2 is negatively linked to TRKB.T1 expression but not TRKB.FL expression. However, the mechanisms behind TrkB.T1 isoform-specific expression and its role in astrocyte development are unknown.

In this study, we used advanced sequencing techniques to analyze DNA methylation patterns, a chemical modification that can control gene activity, in neurons, astrocytes, and microglia, which are three different cell types in the brain. Our study discovered distinct methylation patterns in all three cell types and supported previous research DNA methylation effect on gene regulation and alternative gene splicing. With the data obtain from this study, we also observed a significant difference on DNA methylation may cause that TrkB.T1 mainly expressed in astrocytes and TrkB.FL is mainly expressed in neurons. The study further investigated TrkB.T1 deficient astrocytes at different developmental stages. By examining RNA from astrocytes, we found abnormal gene expression in astrocyte maturation. Further analysis showed changes in cholesterol transport, suggesting potential implications for synapse formation. Finally, we observed the dysregulated spine density in the animals with astrocyte specific TrkB.T1 deletion. These findings suggest that TrkB.T1 deficiency adversely affects normal astrocyte development, which in turn affects neuronal synapse development. These findings provide new insights into the expression mechanisms and functions of TrkB.T1 in astrocytes, enhancing our understanding of how these cells support brain health and function.

Publications

Wei X, Li J, Cheng Z, Wei S, Yu G, Olsen ML. Decoding the Epigenetic Landscape: Insights into 5mC and 5hmC Patterns and Impacts on Gene Regulation in Mouse Cortical Cell Types. BioRxiv

Wei X, Browning JL, Olsen ML. Neuron and astrocyte specific 5mC and 5hmC signatures of BDNF’s receptor, TrkB. Submitted

Wei X, Li J, Olsen ML. The astrocyte transcriptome across the lifespan. In preparation

Wei X, Pan Y, Browning JL, Noel K, Olsen ML. Unveiling the Role of TrkB.T1 in Astrocyte Development and Synapse Formation through Bdnf Signaling. In preparation

Leonard J, Wei X, Gudenschwager-Basso E, Li J, Harris E, Olsen M, Theus M. Transcriptomic alterations in cortical astrocytes following the development of post-traumatic epilepsy. Scientific Reports. 2024 Apr 10;14(1):8367 

Browning JL, Wilson KA, Shandra O, Wei X, Mahmutovic D, Maharathi B, Robel S, VandeVord PJ, Olsen ML. Applying Proteomics and Computational Approaches to Identify Novel Targets in Blast-Associated Post-Traumatic Epilepsy. International Journal of Molecular Sciences. 2024 Mar 1;25(5):2880.

Fritsch LE, Kelly C, Leonard J, de Jager C, Wei X, Brindley S, Harris EA, Kaloss AM, DeFoor N, Paul S, O’Malley H. STING-dependent signaling in microglia or peripheral immune cells orchestrates the early inflammatory response and influences brain injury outcome. Journal of Neuroscience. 2024 Feb 14.

Gudenschwager Basso EK, Ju J, Soliman E, de Jager C, Wei X, Pridham KJ, Olsen ML, Theus MH. Immunoregulatory and neutrophil-like monocyte subsets with distinct single-cell transcriptomic signatures emerge following brain injury. Journal of Neuroinflammation. 2024 Feb 3;21(1):41.

Gudenschwager-Basso EK, Shandra O, Volanth T, Patel DC, Kelly C, Browning JL, Wei X, Harris EA, Mahmutovic D, Kaloss AM, Correa FG. Atypical Neurogenesis, Astrogliosis, and Excessive Hilar Interneuron Loss Are Associated with the Development of Post-Traumatic Epilepsy. Cells. 2023 Apr 25;12(9):1248. 

Xu X, Wei X, Xie H. Advances in methods and software for RNA cytosine methylation analysis. Genomics. 2020 Mar 1;112(2):1840-6. 

Sun Z, Xu X, He J, Murray A, Sun MA, Wei X, Wang X, McCoig E, Xie E, Jiang X, Li L. EGR1 recruits TET1 to shape the brain methylome during development and upon neuronal activity. Nature Communications. 2019 Aug 29;10(1):3892. 

Banerjee S, Wei X, Xie H. Recursive motif analyses identify brain epigenetic transcription regulatory modules. Computational and structural biotechnology journal. 2019 Jan 1;17:507-15. 

Presentations

Wei X, Li J, Cheng Z, Wei S, Yu G and Olsen ML, Genome wide 5mC and 5hmC patterns determine unique transcriptional signatures, transcriptional regulators and alternative splicing of neural cell types in mouse brain. Neuroscience 2023., Nov 2023. Invited Symposium talk

Wei X and Olsen ML, Methylome, transcriptome and alternative splicing profiling of neurons, astrocytes, and microglia. Biology of Genomes 2023, May 2023. 

Wei X and Olsen ML, DNA methylation regulates TrkB isoform expression in CNS. Neuroscience 2022, Nov 2022. 

Wei X, Holt LM, Pacheco NL, Lyu B, Hernandez RD, Yu G and Olsen ML, Transcriptomic Profiling of Astrocyte Development. 52nd Annual ASN Meeting, Roanoke. Apr 2022.

Wei X and Olsen ML, DNA methylation regulates TrkB isoform expression in CNS. Neuroscience 2021, Nov 2021.

Wei X and Olsen ML, DNA methylation regulates TrkB isoform expression in CNS. Genome Informatics 2021, Nov 2021.

Wei X and Olsen ML, DNA methylation regulates TrkB isoform expression in CNS. XV European Meeting on Glial Cells in Health and Disease, Jul 2021. 

Examination Graduate Committee

Major Advisor/Chair:
Michelle Olsen, PhD
Professor and Director
School of Neuroscience

Graduate Advising Committee Members:

Michelle Theus, PhD
Professor
Biomedical Sciences and Pathobiology

Timothy Jarome, PhD
Associate Professor
School of Animal Sciences

Paul Morton, PhD
Assistant Professor
Biomedical Sciences and Pathobiology

Guoqiang Yu, PhD
Professor
Electrical and Computer Engineering