A Time- and Single-cell-resolved Model of Murine Bone Marrow Hematopoiesis

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2024 Jan 6

PMID 38183977

Authors

Iwo Kucinski

Joana Campos

Melania Barile

Francesco Severi

Natacha Bohin

Pedro N Moreira

Lewis Allen

Hannah Lawson

Myriam L R Haltalli

Sarah J Kinston

Donal OCarroll

Kamil R Kranc

Berthold Gottgens

Affiliations

Soon will be listed here.

Abstract

The paradigmatic hematopoietic tree model is increasingly recognized to be limited, as it is based on heterogeneous populations largely defined by non-homeostatic assays testing cell fate potentials. Here, we combine persistent labeling with time-series single-cell RNA sequencing to build a real-time, quantitative model of in vivo tissue dynamics for murine bone marrow hematopoiesis. We couple cascading single-cell expression patterns with dynamic changes in differentiation and growth speeds. The resulting explicit linkage between molecular states and cellular behavior reveals widely varying self-renewal and differentiation properties across distinct lineages. Transplanted stem cells show strong acceleration of differentiation at specific stages of erythroid and neutrophil production, illustrating how the model can quantify the impact of perturbations. Our reconstruction of dynamic behavior from snapshot measurements is akin to how a kinetoscope allows sequential images to merge into a movie. We posit that this approach is generally applicable to understanding tissue-scale dynamics at high resolution.

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