CellRank for directed single-cell fate mapping

Lange M, Bergen V, Klein M, Setty M, Reuter B, Bakhti M, Lickert H, Ansari M, Schniering J, Schiller HB, Pe'Er D, Theis FJ (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Nature Methods Nature Publishing Group

Book Volume: 19

Pages Range: 159-170

Journal Issue: 2

DOI: 10.1038/s41592-021-01346-6

Abstract

Computational trajectory inference enables the reconstruction of cell state dynamics from single-cell RNA sequencing experiments. However, trajectory inference requires that the direction of a biological process is known, largely limiting its application to differentiating systems in normal development. Here, we present CellRank (https://cellrank.org) for single-cell fate mapping in diverse scenarios, including regeneration, reprogramming and disease, for which direction is unknown. Our approach combines the robustness of trajectory inference with directional information from RNA velocity, taking into account the gradual and stochastic nature of cellular fate decisions, as well as uncertainty in velocity vectors. On pancreas development data, CellRank automatically detects initial, intermediate and terminal populations, predicts fate potentials and visualizes continuous gene expression trends along individual lineages. Applied to lineage-traced cellular reprogramming data, predicted fate probabilities correctly recover reprogramming outcomes. CellRank also predicts a new dedifferentiation trajectory during postinjury lung regeneration, including previously unknown intermediate cell states, which we confirm experimentally.

Involved external institutions

Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE) Memorial Sloan Kettering Cancer Center US United States (USA) (US) Eberhard Karls Universität Tübingen DE Germany (DE)

How to cite

APA:

Lange, M., Bergen, V., Klein, M., Setty, M., Reuter, B., Bakhti, M.,... Theis, F.J. (2022). CellRank for directed single-cell fate mapping. Nature Methods, 19(2), 159-170. https://doi.org/10.1038/s41592-021-01346-6

MLA:

Lange, Marius, et al. "CellRank for directed single-cell fate mapping." Nature Methods 19.2 (2022): 159-170.

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