Publication

Population snapshots predict early haematopoietic and erythroid hierarchies

Tusi, Betsabeh Khoramian
Wolock, Samuel L
Weinreb, Caleb
Hwang, Yung
Hidalgo, Daniel
Zilionis, Rapolas
Waisman, Ari
Huh, Jun R
Klein, Allon M
Socolovsky, Merav
Embargo Expiration Date
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.

Source

Tusi BK, Wolock SL, Weinreb C, Hwang Y, Hidalgo D, Zilionis R, Waisman A, Huh JR, Klein AM, Socolovsky M. Population snapshots predict early haematopoietic and erythroid hierarchies. Nature. 2018 Mar 1;555(7694):54-60. doi: 10.1038/nature25741. Epub 2018 Feb 21. PMID: 29466336; PMCID: PMC5899604.

Year of Medical School at Time of Visit
Sponsors
Dates of Travel
DOI
10.1038/nature25741
PubMed ID
29466336
Other Identifiers
Notes
Funding and Acknowledgements
Corresponding Author
Related Resources
Related Resources
Repository Citation
Rights
Distribution License