Population snapshots predict early haematopoietic and erythroid hierarchies
Nature, 2018•nature.com
The formation of red blood cells begins with the differentiation of multipotent haematopoietic
progenitors. Reconstructing the steps of this differentiation represents a general challenge in
stem-cell biology. Here we used single-cell transcriptomics, fate assays and a theory that
allows the prediction of cell fates from population snapshots to demonstrate that mouse
haematopoietic progenitors differentiate through a continuous, hierarchical structure into
seven blood lineages. We uncovered coupling between the erythroid and the basophil or …
progenitors. Reconstructing the steps of this differentiation represents a general challenge in
stem-cell biology. Here we used single-cell transcriptomics, fate assays and a theory that
allows the prediction of cell fates from population snapshots to demonstrate that mouse
haematopoietic progenitors differentiate through a continuous, hierarchical structure into
seven blood lineages. We uncovered coupling between the erythroid and the basophil or …
Abstract
The formation of red blood cells begins with the differentiation of multipotent haematopoietic progenitors. Reconstructing the steps of this differentiation represents a general challenge in stem-cell biology. Here we used single-cell transcriptomics, fate assays and a theory that allows the prediction of cell fates from population snapshots to demonstrate that mouse haematopoietic progenitors differentiate through a continuous, hierarchical structure into seven blood lineages. We uncovered coupling between the erythroid and the basophil or mast cell fates, a global haematopoietic response to erythroid stress and novel growth factor receptors that regulate erythropoiesis. We defined a flow cytometry sorting strategy to purify early stages of erythroid differentiation, completely isolating classically defined burst-forming and colony-forming progenitors. We also found that the cell cycle is progressively remodelled during erythroid development and during a sharp transcriptional switch that ends the colony-forming progenitor stage and activates terminal differentiation. Our work showcases the utility of linking transcriptomic data to predictive fate models, and provides insights into lineage development in vivo.
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