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Fischer, D.S. ; Fiedler, A. ; Kernfeld, E.M.* ; Genga, R.M.J.* ; Bastidas-Ponce, A. ; Bakhti, M. ; Lickert, H. ; Hasenauer, J. ; Maehr, R.* ; Theis, F.J.

Inferring population dynamics from single-cell RNA-sequencing time series data.

Nat. Biotechnol. 37, 461-468 (2019)
Postprint DOI PMC
Open Access Green
Recent single-cell RNA-sequencing studies have suggested that cells follow continuous transcriptomic trajectories in an asynchronous fashion during development. However, observations of cell flux along trajectories are confounded with population size effects in snapshot experiments and are therefore hard to interpret. In particular, changes in proliferation and death rates can be mistaken for cell flux. Here we present pseudodynamics, a mathematical framework that reconciles population dynamics with the concepts underlying developmental trajectories inferred from time-series single-cell data. Pseudodynamics models population distribution shifts across trajectories to quantify selection pressure, population expansion, and developmental potentials. Applying this model to time-resolved single-cell RNA-sequencing of T-cell and pancreatic beta cell maturation, we characterize proliferation and apoptosis rates and identify key developmental checkpoints, data inaccessible to existing approaches.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Parameter-estimation; Gene-expression; Beta-cells; Identification; Islets; Fate
ISSN (print) / ISBN 1087-0156
e-ISSN 1546-1696
Zeitschrift Nature Biotechnology
Quellenangaben Band: 37, Heft: 4, Seiten: 461-468 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort New York, NY
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
Institute of Diabetes and Regeneration Research (IDR)