@article {Dussiau2021.04.30.442092, author = {Charles Dussiau and Agathe Boussaroque and Mathilde Gaillard and Clotilde Bravetti and Laila Zaroili and Camille Knosp and Chlo{\'e} Friedrich and Philippe Asquier and Lise Willems and Laurent Quint and Didier Bouscary and Michaela Fontenay and Thibault Espinasse and Adriana Plesa and Pierre Sujobert and Olivier Gandrillon and Olivier Kosmider}, title = {Hematopoietic differentiation is characterized by a transient peak of cell-to-cell gene expression variability in normal and pathological conditions}, elocation-id = {2021.04.30.442092}, year = {2021}, doi = {10.1101/2021.04.30.442092}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Hematopoietic differentiation has been considered as a multistep process which is metaphorically represented as linear trajectories with discrete steps from hematopoietic stem cells to mature cells. While the transcriptional state of cells at the beginning or at the end of these trajectories are relatively well described from bulk analysis, what happens in the intermediate states has remained elusive until the use of single cell approaches allowed to capture the dynamic changes of transcriptomic states.Applying Shannon entropy to measure cell-to-cell variability among cells at the same stage of differentiation, we observed a transient peak of gene expression variability in all the hematopoietic differentiation pathways. Strikingly, genes with the highest entropy variation in a given differentiation pathway matched genes known as pathway-specific, whereas genes with the highest expression variation were common to all pathways. Finally, we showed that the level of cell-to-cell variation is increased in the most immature compartment of hematopoiesis in myelodysplastic syndromes.These data suggest that differentiation may not be as deterministic and linear as previously thought, but could be better conceptualized as a dynamical stochastic process with a transient stage of cellular indetermination.Competing Interest StatementThe authors have declared no competing interest.}, URL = {https://www.biorxiv.org/content/early/2021/04/30/2021.04.30.442092}, eprint = {https://www.biorxiv.org/content/early/2021/04/30/2021.04.30.442092.full.pdf}, journal = {bioRxiv} }