image: Fluorescent imaging of a zebrafish embryo highlights cell populations during early development. The image reflects the type of dynamic biological system researchers used to test RegVelo, a new AI framework for predicting how cells acquire their identities and identifying the genetic regulators that guide them.
Credit: Stowers Institute for Medical Research
Scientists at the Stowers Institute for Medical Research, Helmholtz Munich, the Technical University of Munich, and the University of Oxford have developed RegVelo — a new AI framework that simultaneously models cellular dynamics and gene regulation, enabling researchers to predict, simulate, and experimentally validate how cells make fate decisions. The study is published in Cell on May 11, 2026.
Kansas City, Mo., USA, and Munich, Germany — May 11, 2026 — How does a single cell know to become a pigment cell, a blood cell, or a neuron? Scientists have long been able to map where cells are headed. What has remained far harder is understanding which molecular regulators steer them there — and what happens when those regulators are altered.
Now, a team of researchers has developed RegVelo, an AI-based model that closes that gap. Published May 11, 2026, in Cell, the framework jointly learns how cells change over time and which gene regulatory networks drive those changes — making it possible to model both the trajectory and the molecular engine behind it.
Connecting two fields that have worked in parallel
Single-cell biology has given researchers increasingly detailed maps of development. RNA velocity methods estimate how cells move through developmental landscapes; gene regulatory network approaches identify the relationships among genes. Until now, these methods have largely been used in parallel rather than together.
RegVelo bridges that divide. Building on RNA velocity — which infers a cell’s direction of change from the ratio of immature to processed RNA — the model adds a critical layer: It accounts for genes not as independent units but as parts of a network, where each gene can activate or suppress others. The result is a framework that can trace developmental trajectories and simulate the consequences of specific regulatory interventions.
“For a long time, cellular dynamics and gene regulation have largely been modeled separately,” said Prof. Fabian J. Theis, co-senior author of the study and Director of the Computational Health Center (CHC) at Helmholtz Munich and Professor at the Technical University of Munich (TUM). “RegVelo brings those pieces together, allowing us to ask not only how cells are changing, but which regulatory interactions are helping drive those changes.”
A collaboration built on complementary strengths
RegVelo emerged from a collaboration that integrated experimental and computational expertise across institutions. Tatjana Sauka-Spengler, Ph.D., co-senior author and Investigator at the Stowers Institute for Medical Research, moved her lab to Stowers from the University of Oxford in 2022. Sauka-Spengler, who remains a Visiting Researcher at the MRC Weatherall Institute of Molecular Medicine, University of Oxford, contributed high-resolution gene regulatory circuitry from her team’s research on cranial neural crest development. Theis’s group at Helmholtz Munich brought computational tools for modeling single-cell trajectories and RNA velocity. First author Weixu Wang, a doctoral researcher at the CHC, led the development of the unified deep learning framework.
“What made this work especially powerful was the combination of complementary strengths,” said Sauka-Spengler. “High-resolution gene regulatory circuitry from our lab, and dynamic trajectory and network modeling from Fabian’s team, who are experts in what they do. RegVelo emerged from integrating those two views into one framework for the first time.”
Predictions validated in zebrafish
The team tested RegVelo across multiple biological systems, including the cell cycle, blood cell formation, and pancreatic development. The most detailed case study focused on zebrafish neural crest cells — a versatile population of embryonic cells that give rise to pigment cells, nerve cells, and craniofacial tissues.
RegVelo identified tfec as an early driver of pigment cell development and revealed elf1 as a previously unknown regulator of pigment cell fate. Both predictions were validated experimentally through CRISPR/Cas9 knockout and single-cell Perturb-seq, demonstrating that the model can generate biologically meaningful hypotheses that hold up in living systems.
“Development is often described as a series of static snapshots of cell states,” said Sauka-Spengler. “What we really want to understand is how cells make decisions — how they transition from one state to another. RegVelo models how those fate decisions are encoded in gene regulatory networks over time, and what drives them.”
“RegVelo makes visible what consequences it has for a cell’s developmental path when a specific genetic regulator is switched off,” said Wang. “Verifiable predictions can be derived from single-cell data about which genetic regulators promote, slow down, or redirect a particular developmental path.”
A step toward virtual cell models
The researchers describe RegVelo as a step toward a more predictive form of developmental biology, one in which computational models help prioritize experiments, uncover hidden regulators, and forecast how cell fates may shift when gene networks are perturbed. Looking further ahead, the approach could help researchers better understand disease-relevant cell states and identify new therapeutic targets — including in developmental disorders, cancer biology, and regenerative medicine.
“RegVelo is a step toward virtual cell models that will help us better understand how cells behave in differentiation contexts and how they respond to genetic perturbation,” said Theis. “In the long term, this could help us identify possible starting points for new therapies.”
“Having a full resolution of gene regulatory circuitry that has been predicted, simulated, perturbed, and validated gives us a very solid tool,” Sauka-Spengler added. “We can start from stem cells or naïve cells and develop new ways of directing them toward cell types that can be used in cell therapies.”
Institutional press releases with additional background, broadcast-quality videos/images, and researcher profiles/headshots are available from the Stowers Institute and Helmholtz Munich. All can be found in this multimedia folder.
Video: Predicting cell fate, hear from the scientists behind the work
Video: Tatjana Sauka-Spengler, Ph.D., on decoding the cell's instructions
Additional Authors include Zhiyuan Hu, Philipp Weiler, Sarah Mayes, Marius Lange, Daniel M. Fountain, Julianna O. Haug, Jingye Wang, and Zhengyuan Xue.
This work was co-funded by the European Union (ERC, DeepCell – 101054957), the Wellcome Leap ΔTissue Program (9E8E84F7-8991-4D4A-A9EC), the European Union’s Horizon 2022 programme (Grant No. 101057775), the German Federal Ministry of Education and Research through the HOPARL project (031L0289A), the DFG Graduate School of QBM (GSC 1006), the Joachim Herz Foundation, an EMBO Postdoctoral Fellowship, the Wellcome Trust Award #215615/Z/19/Z, Stowers Institute for Medical Research institutional support to T.S.S., the Fundamental Research Funds for the Central Universities (2042025kf0022, 2042022dx0003), and the National Natural Science Foundation of China (32500725).
About the Stowers Institute for Medical Research
Founded in 1994 through the generosity of Jim Stowers, founder of American Century Investments, and his wife, Virginia, the Stowers Institute for Medical Research is a non-profit, biomedical research organization with a focus on foundational research. Its mission is to expand our understanding of the secrets of life and improve life’s quality through innovative approaches to the causes, treatment, and prevention of diseases.
The Institute consists of 24 independent research programs. Of the approximately 500 members, over 370 are scientific staff that include principal investigators, technology center directors, postdoctoral scientists, graduate students, and technical support staff. Learn more about the Institute at www.stowers.org and about its graduate program at www.stowers.org/gradschool.
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About Helmholtz Munich
Helmholtz Munich is a leading biomedical research center. Its mission is to develop breakthrough solutions for better health in a rapidly changing world. Interdisciplinary research teams focus on environmentally triggered diseases, especially the therapy and prevention of diabetes, obesity, allergies, and chronic lung diseases. With the power of artificial intelligence and bioengineering, researchers accelerate the translation to patients. Helmholtz Munich has more than 2,550 employees and is headquartered in Munich/Neuherberg. It is a member of the Helmholtz Association, with more than 46,000 employees and 18 research centers the largest scientific organization in Germany. More about Helmholtz Munich (Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH): www.helmholtz-munich.de/en
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About the MRC Weatherall Institute of Molecular Medicine
The MRC Weatherall Institute of Molecular Medicine (MRC WIMM) at the University of Oxford was founded in 1989 by Sir David Weatherall to advance research in molecular and cellular medicine and improve human health. The institute is part of the Radcliffe Department of Medicine and brings together researchers from across the Medical Sciences Division to drive interdisciplinary collaboration. MRC WIMM is internationally recognised for its strengths in basic and translational research, contributing to advances in the understanding, diagnosis, and treatment of a wide range of human diseases. https://www.imm.ox.ac.uk/
About the Radcliffe Department of Medicine
The Radcliffe Department of Medicine’s vision is to use science to support a healthier, longer life for all. It aims to improve health through cross-disciplinary research to understand shared mechanisms of disease and to accelerate the transition from scientific discovery to clinical care. RDM has internationally renowned programmes in cardiovascular and metabolic medicine, as well as molecular medicine, including immunology and haematology.’ https://www.rdm.ox.ac.uk/
Journal
Cell
Subject of Research
Animals
Article Title
RegVelo: gene-regulatory-informed dynamics of single cells
Article Publication Date
11-May-2026