New tool to map the origins and journeys of cells in development and disease
Listen to this news story:
A new computational tool allows researchers to understand how the diverse cell types of the human body are made during development, and how diseases progress over time at the cellular level.
Researchers from the Wellcome Sanger Institute and the German Cancer Research Center developed ‘cell2fate’.1 Published today (3 March) in Nature Methods, cell2fate helps researchers map cellular trajectories – the sequence of cell fate changes that results in a mature and functioning cell type. It also reveals altered cellular trajectories in various diseases such as brain tumours, helping to identify new potential targets for therapies.
Previous models that analyse cell trajectories are limited in function, so researchers have not been able to investigate the changing nature of gene expression over the course of complex cell trajectories.
Therefore, in this new study, the scientists’ key innovation was to make an accurate model of the biophysical dynamics of gene expression.
Cell2fate uses data from single cell RNA sequencing experiments, where all of the genes turned on, or ‘expressed’ in each cell in a tissue are measured. Cell2fate breaks down complex cellular trajectories into shorter phases described as modules. It then separately models the gene expression dynamics of each module and stitches these modules together.
In doing so, cell2fate can help reconstruct complex cellular trajectories during development and disease, and identify potential molecular regulators of these trajectories. This innovative approach gives cell2fate much more power than previous models.
The researchers used cell2fate to identify novel stages of the development of a specific kind of neuron found in the hippocampus of the brain, the area involved in learning and memory. Cell2fate revealed new gene expression programmes regulating the final maturation of these neurons – this ‘code’ for how the brain makes hippocampal neurons is an incredibly useful resource for future studies that look into the development of diseases.
As part of ongoing follow up work, the team is applying cell2fate to reconstruct cellular trajectories in brain tumours. Very little is known about how cancer cells change during the progression of the disease, and whether different tumours follow the same trajectories. Cell2fate will be a powerful tool to unpick these clinical mysteries.
“Cell2fate is an innovative tool because it digs deep into the complexity of the time-specific phases of cell maturation, and that hasn’t been achieved before. Older models have a tendency to oversimplify the process of cell trajectories, and so we are excited to be able to share a cutting-edge tool that can be applied to new datasets and uncover findings in a more detailed and accurate way.”
Dr Alexander Aivazidis, first author at the European Molecular Biology Laboratory (EMBL) and formerly at the Wellcome Sanger Institute
“Whilst we have shown that cell2fate is a reliable tool to investigate maturing cells, more generally our study also highlights how looking at RNA velocity modules, which are short successive phases of transcription, is a promising way of studying cellular biology. We look forward to our tool being used more widely in order to develop a deeper understanding of the intricacies of how our stem cells gradually develop into different functioning cells.”
Dr Oliver Stegle, co-senior author and Head of the Division of Computational Genomics and System Genetics at the German Cancer Researcher Center
“Cell2fate has already shown to be a useful tool to look at the dynamics of stem cells as they develop into cells with particular functions. We are now interested in using cell2fate to unravel the details of what controls cellular changes in a disease context. For example, in the long run, we want to help identify the genes that control cancer cell trajectories in brain tumours so we can think about how we can intervene at these stages to prevent these cancers forming in the first place.”
Dr Omer Ali Bayraktar, senior author and a Group Leader at the Wellcome Sanger Institute
More information
Footnotes
- For more information on cell2fate and where to find the tool, follow this link: GitHub – BayraktarLab/cell2fate: Inference of RNA velocity modules for prediction of cell fates and integration with spatial and regulatory models.
Publication:
Alexander Aivazidis et al. (2025) ‘Inference of RNA velocity modules improves cell fate prediction.’ Nature Methods. DOI: 10.1038/s41592-025-02608-3
Funding:
This research was supported by Wellcome. Full details can be found in the publication.
