More or less - on the influence of labelling strategies to infer cell population dynamics

• Verfasst von: Gabel, Michael [VerfasserIn]
• Verfasst von: Regös, Roland Robert [VerfasserIn]
• Verfasst von: Graw, Frederik [VerfasserIn]
• Titel: More or less - on the influence of labelling strategies to infer cell population dynamics
• Verf.angabe: Michael Gabel, Roland R. Regoes, Frederik Graw
• E-Jahr: 2017
• Jahr: October 18, 2017
• Umfang: Illustrationen
• Umfang: 17 S.
• Fussnoten: Gesehen am 06.06.2018
• Titel Quelle: Enthalten in: PLOS ONE
• Ort Quelle: San Francisco, California, US : PLOS, 2006
• Jahr Quelle: 2017
• Band/Heft Quelle: 12(2017,10), Artikelnummer e0185523, 17 Seiten
• ISSN Quelle: 1932-6203
• DOI: doi:10.1371/journal.pone.0185523
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Adoptive transfer
• Sach-SW: Cell activation
• Sach-SW: Cell death
• Sach-SW: Cell differentiation
• Sach-SW: Cell proliferation
• Sach-SW: Population dynamics
• Sach-SW: Precursor cells
• Sach-SW: T cells
• K10plus-PPN: 1576026426

Abstract

The adoptive transfer of labelled cell populations has been an essential tool to determine and quantify cellular dynamics. The experimental methods to label and track cells over time range from fluorescent dyes over congenic markers towards single-cell labelling techniques, such as genetic barcodes. While these methods have been widely used to quantify cell differentiation and division dynamics, the extent to which the applied labelling strategy actually affects the quantification of the dynamics has not been determined so far. This is especially important in situations where measurements can only be obtained at a single time point, as e.g. due to organ harvest. To this end, we studied the appropriateness of various labelling strategies as characterised by the number of different labels and the initial number of cells per label to quantify cellular dynamics. We simulated adoptive transfer experiments in systems of various complexity that assumed either homoeostatic cellular turnover or cell expansion dynamics involving various steps of cell differentiation and proliferation. Re-sampling cells at a single time point, we determined the ability of different labelling strategies to recover the underlying kinetics. Our results indicate that cell transition and expansion rates are differently affected by experimental shortcomings, such as loss of cells during transfer or sampling, dependent on the labelling strategy used. Furthermore, uniformly distributed labels in the transferred population generally lead to more robust and less biased results than non-equal label sizes. In addition, our analysis indicates that certain labelling approaches incorporate a systematic bias for the identification of complex cell expansion dynamics.