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Research: Molecular and genetic landscapes of retina and brain microglia in neurodegenerative diseases
- Khang Ma and
- Rinki Ratnapriya
Genome Res. October 2025 35: 2143-2157; Published in Advance August 26, 2025, doi:10.1101/gr.280554.125
...-driven dysregulation has emerged as a significant underlying mechanism in many neurodegenerative diseases, such as age-related macular degeneration (AMD) and Alzheimer's disease (AD). Although both brain and retinal microglia originate from the yolk sac, it is uncertain whether they share molecular similarities...
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Resource: Single-nucleus multiomic profiling of the aging mouse substantia nigra reveals conserved gene alterations linked to Parkinson's disease
- Kangli Wang,
- Weikun Xia,
- Yingli Gu,
- Songpeng Zu,
- Qian Yang,
- Maria Luisa Amaral,
- Yaozhi Wang,
- Allen Wang,
- Xiang-Dong Fu,
- William C. Mobley,
- and Bing Ren
Genome Res. March 4, 2026 gr.281113.125; Published in Advance March 4, 2026, doi:10.1101/gr.281113.125
...consistently differentially expressed with aging and PD. Key genes 32 such as Hsp90aa1 and Hsp90ab1 are upregulated at late aging stages in oligodendrocytes, 33 microglia, and glutamatergic neurons. Additionally, Apoe in microglia and genes related to 34 protein folding in oligodendrocytes are upregulated...
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Mini-Review: The paradox of R-loops: guardians of the genome or drivers of disease?
- Shachinthaka D. Dissanayaka Mudiyanselage,
- Phillip Wulfridge,
- and Kavitha Sarma
Genome Res. September 2025 35: 1919-1928; Published in Advance August 6, 2025, doi:10.1101/gr.278992.124
...is unclear.When not properly regulated, R-loops can become a significant source of genomic instability and can activate inflammatory immune responses (Brickner et al. 2022). However, R-loops also play roles in cellular processes, including transcription, DNA replication, DNA repair, and chromosome...
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Method: Identification of the shortest species-specific oligonucleotide sequences
- Ioannis Mouratidis,
- Maxwell A. Konnaris,
- Nikol Chantzi,
- Candace S.Y. Chan,
- Michail Patsakis,
- Kimonas Provatas,
- Austin Montgomery,
- Fotis A. Baltoumas,
- Congzhou M. Sha,
- Manvita Mareboina,
- Georgios A. Pavlopoulos,
- Dionysios V. Chartoumpekis,
- and Ilias Georgakopoulos-Soares
Genome Res. February 2025 35: 279-295; Published in Advance January 2, 2025, doi:10.1101/gr.280070.124
..., nucleic quasi-prime genes account for a significantly larger proportion of the variation based on average gene expression. Nonneuronal cell types, including astrocytes, endothelial cells, microglia perivascular-macrophages, oligodendrocytes, and vascular and leptomeningeal cells, exhibit significant...
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Resource: Dynamic dysregulation of retrotransposons in neurodegenerative diseases at the single-cell level
- Wankun Deng,
- Citu Citu,
- Andi Liu,
- and Zhongming Zhao
Genome Res. October 2024 34: 1687-1699; Published in Advance October 18, 2024, doi:10.1101/gr.279363.124
...of the aged population, neurodegenerative diseases, particularly Alzheimer's disease (AD), have become a significant public health challenge (Mayeux and Stern 2012). Extensive research has been conducted to unravel cellular heterogeneity in neurodegenerative diseases including AD, Parkinson's disease (PD...
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Research: Transcriptional programs mediating neuronal toxicity and altered glial–neuronal signaling in a Drosophila knock-in tauopathy model
- Hassan Bukhari,
- Vanitha Nithianandam,
- Rachel A. Battaglia,
- Anthony Cicalo,
- Souvarish Sarkar,
- Aram Comjean,
- Yanhui Hu,
- Matthew J. Leventhal,
- Xianjun Dong,
- and Mel B. Feany
Genome Res. April 2024 34: 590-605; Published in Advance April 10, 2024, doi:10.1101/gr.278576.123
...heterozygous or homozygous for Tau P251L display age-dependent neurodegeneration, display metabolic defects, and accumulate DNA damage in affected neurons. To understand the molecular events promoting neuronal dysfunction and death in knock-in flies, we performed single-cell RNA sequencing on approximately 130...
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Method: A unified analysis of atlas single-cell data
- Hao Chen,
- Nam D. Nguyen,
- Matthew Ruffalo,
- and Ziv Bar-Joseph
Genome Res. May 2025 35: 1219-1233; Published in Advance February 18, 2025, doi:10.1101/gr.279631.124
...(ENS) neurons (Furness 2012), whereas immune-related GO categories (e.g., GO:0002682 regulation of immune system process, GO:0046649 lymphocyte activation) are mostly associated with immune cells, such as myeloid cells (Gupta et al. 2014), lymphoid cells (Blom and Spits 2006), and microglia (Graeber...
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Resource: Remodeling of epigenome and transcriptome landscapes with aging in mice reveals widespread induction of inflammatory responses
- Bérénice A. Benayoun,
- Elizabeth A. Pollina,
- Param Priya Singh,
- Salah Mahmoudi,
- Itamar Harel,
- Kerriann M. Casey,
- Ben W. Dulken,
- Anshul Kundaje,
- and Anne Brunet
Genome Res. April 2019 29: 697-709; Published in Advance March 11, 2019, doi:10.1101/gr.240093.118
...in four tissues and one cell type during mouse aging. (A) Experimental setup (see Supplemental Table S1). (B) Example browser region showing tracks of data sets in cerebellum tissue at different ages. (Chr) Chromosome. (C–F) Multidimensional scaling analysis results across data sets based on RNA...
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Research: Suppressor mutations in Mecp2-null mice implicate the DNA damage response in Rett syndrome pathology
- Adebola Enikanolaiye,
- Julie Ruston,
- Rong Zeng,
- Christine Taylor,
- Marijke Schrock,
- Christie M. Buchovecky,
- Jay Shendure,
- Elif Acar,
- and Monica J. Justice
Genome Res. April 2020 30: 540-552; Published in Advance April 21, 2020, doi:10.1101/gr.258400.119
..., including intellectual disabilities, autism, neuropsychiatric disorders, and lupus erythematosus (Neul and Zoghbi 2004; Bienvenu and Chelly 2006). The type of MECP2 mutation does not always correlate with disease severity, in part, because of skewing of X Chromosome inactivation in heterozygous females...
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Perspective: Applications of single-cell genomics and computational strategies to study common disease and population-level variation
- Benjamin J. Auerbach,
- Jian Hu,
- Muredach P. Reilly,
- and Mingyao Li
Genome Res. October 2021 31: 1728-1741; doi:10.1101/gr.275430.121
...in AD (Buttner et al. 2020), and an increase of microglia in advanced age-related macular degeneration (Lyu et al. 2021).Computational analysis and considerations for population-based single-cell studiesIn this section, we describe analytical strategies of population-based single-cell studies...
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