RT Journal Article
SR Electronic
T1 Hematopoietic differentiation is characterized by a transient peak of cell-to-cell gene expression variability in normal and pathological conditions
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.04.30.442092
DO 10.1101/2021.04.30.442092
A1 Charles Dussiau
A1 Agathe Boussaroque
A1 Mathilde Gaillard
A1 Clotilde Bravetti
A1 Laila Zaroili
A1 Camille Knosp
A1 Chloé Friedrich
A1 Philippe Asquier
A1 Lise Willems
A1 Laurent Quint
A1 Didier Bouscary
A1 Michaela Fontenay
A1 Thibault Espinasse
A1 Adriana Plesa
A1 Pierre Sujobert
A1 Olivier Gandrillon
A1 Olivier Kosmider
YR 2021
UL http://biorxiv.org/content/early/2021/04/30/2021.04.30.442092.abstract
AB 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.