Linking gene start sites, DNA methylation, and open chromatin to RNA splicing in single cells
Multiome measurements connecting transcription start sites at single-nucleotide resolution, DNA methylation and open chromatin status to splicing outcome across single cells in health and disease
['FUNDING_OTHER'] · WEILL MEDICAL COLL OF CORNELL UNIV · NIH-11290340
This project uses advanced single-cell sequencing to map how where genes start, DNA methylation, and chromatin openness affect RNA splicing in adult brain and other tissues, with relevance for diseases like frontotemporal dementia.
Quick facts
| Phase | ['FUNDING_OTHER'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | WEILL MEDICAL COLL OF CORNELL UNIV (nih funded) |
| Locations | 1 site (NEW YORK, UNITED STATES) |
| Trial ID | NIH-11290340 on ClinicalTrials.gov |
What this research studies
Researchers will apply long-read single-cell and single-nucleus sequencing methods to human and mouse tissues to read full RNA isoforms and connect them to exact transcription start sites. They will combine that RNA information with measurements of DNA methylation and chromatin accessibility in the same cell types to see how those features influence splicing. The work builds on methods the team developed to profile thousands of single cells and to study frozen tissues, and it includes comparisons between healthy and diseased brains. Results aim to reveal splicing changes that occur in specific cell subtypes and developmental stages.
Who could benefit from this research
Good fit: Ideal participants would be adults connected to brain-tissue donation programs or adults with neurodegenerative conditions such as frontotemporal dementia who are willing to provide clinical data or biospecimens.
Not a fit: People seeking immediate new treatments, children, or adults without neurological conditions are unlikely to see a direct personal benefit from this project.
Why it matters
Potential benefit: If successful, this work could reveal cell-type specific splicing changes that become biomarkers or targets for neurological diseases such as frontotemporal dementia.
How similar studies have performed: The team has already developed and published long-read single-cell isoform sequencing methods and used them to find splicing dysregulation in frontotemporal dementia, though combining these data with matched methylation and chromatin measures is newer.
Where this research is happening
NEW YORK, UNITED STATES
- WEILL MEDICAL COLL OF CORNELL UNIV — NEW YORK, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: TILGNER, HAGEN ULRICH — WEILL MEDICAL COLL OF CORNELL UNIV
- Study coordinator: TILGNER, HAGEN ULRICH
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.