Quantifying the Dynamics of Hematopoiesis by In Vivo IdU Pulse-Chase, Mass Cytometry, and Mathematical Modeling

Amir Erez, Ratnadeep Mukherjee, Grégoire Altan-Bonnet*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

We present a new method to directly quantify the dynamics of differentiation of multiple cellular subsets in unperturbed mice. We combine a pulse-chase protocol of 5-iodo-2′-deoxyuridine (IdU) injections with subsequent analysis by mass cytometry (CyTOF) and mathematical modeling of the IdU dynamics. Measurements by CyTOF allow for a wide range of cells to be analyzed at once, due to the availability of a large staining panel without the complication of fluorescence spillover. These are also compatible with direct detection of integrated iodine signal, with minimal impact on immunophenotyping based on the surface markers. Mathematical modeling beyond a binary classification of surface marker abundance allows for a continuum of cellular states as the cells transition from one state to another. Thus, we present a complete and robust method for directly quantifying differentiation at the systemic level, allowing for system-wide comparisons between different mouse strains and/or experimental conditions. Published 2019. This article is a U.S. Government work and is in the public domain in the USA.

Original languageAmerican English
Pages (from-to)1075-1084
Number of pages10
JournalCytometry. Part A : the journal of the International Society for Analytical Cytology
Volume95
Issue number10
DOIs
StatePublished - 1 Oct 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
Published 2019. This article is a U.S. Government work and is in the public domain in the USA.

Keywords

  • B-cells
  • CyTOF
  • IdU
  • bone marrow
  • differentiation
  • hematopoiesis
  • neutrophils

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