Hematopoietic differentiation is characterized by a transient peak of cell-to-cell gene expression variability in normal and pathological conditions
Hematopoietic differentiation is characterized by a transient peak of cell-to-cell gene expression variability in normal and pathological conditions
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.
Kosmider Olivier、Gaillard Mathilde、Zaroili Laila、Knosp Camille、Friedrich Chlo¨|、Asquier Philippe、Fontenay Michaela、Plesa Adriana、Gandrillon Olivier、Sujobert Pierre、Bouscary Didier、Espinasse Thibault、Quint Laurent、Boussaroque Agathe、Bravetti Clotilde、Willems Lise、Dussiau Charles
Universit¨| de Paris, Institut Cochin, CNRSUMR8104, INSERM U1016, A Member of OPALE Carnot Institute, The Organization for Partnerships in Leukemia||Assistance Publique-H?pitaux de Paris. Centre - Universit¨| de Paris, Service d?ˉH¨|matologie biologique, H?pital CochinUniv Lyon, ENS de Lyon, Universit¨| Claude Bernard, CNRS UMR 5239, INSERM U1210, Laboratory of Biology and Modelling of the CellUniversit¨| de Paris, Institut Cochin, CNRSUMR8104, INSERM U1016, A Member of OPALE Carnot Institute, The Organization for Partnerships in LeukemiaUniversit¨| de Paris, Institut Cochin, CNRSUMR8104, INSERM U1016, A Member of OPALE Carnot Institute, The Organization for Partnerships in LeukemiaUniversit¨| de Paris, Institut Cochin, CNRSUMR8104, INSERM U1016, A Member of OPALE Carnot Institute, The Organization for Partnerships in Leukemia||Assistance Publique-H?pitaux de Paris. Centre - Universit¨| de Paris, Service d?ˉH¨|matologie biologique, H?pital CochinPole Sante Vinci 1 Avenue Du Pr Alexandre MinkowskiUniversit¨| de Paris, Institut Cochin, CNRSUMR8104, INSERM U1016, A Member of OPALE Carnot Institute, The Organization for Partnerships in Leukemia||Assistance Publique-H?pitaux de Paris. Centre - Universit¨| de Paris, Service d?ˉH¨|matologie biologique, H?pital CochinHospices Civils de Lyon, H?pital Lyon Sud, Service d?ˉH¨|matologie Biologique||Cancer Research Center of LyonUniv Lyon, ENS de Lyon, Universit¨| Claude Bernard, CNRS UMR 5239, INSERM U1210, Laboratory of Biology and Modelling of the Cell||Inria Team Dracula, Inria Center Grenoble Rh?ne-AlpesHospices Civils de Lyon, H?pital Lyon Sud, Service d?ˉH¨|matologie Biologique||Cancer Research Center of LyonUniversit¨| de Paris, Institut Cochin, CNRSUMR8104, INSERM U1016, A Member of OPALE Carnot Institute, The Organization for Partnerships in Leukemia||Assistance Publique-H?pitaux de Paris, Centre-Universit¨| de Paris, Service d?ˉH¨|matologie Clinique, H?pital CochinUniv Lyon, Universit¨| Lyon 1, CNRS UMR5208, Institut Camille Jordan||Inria Team Dracula, Inria Center Grenoble Rh?ne-AlpesAssistance Publique-H?pitaux de Paris, Centre-Universit¨| de Paris, Service d?ˉH¨|matologie Clinique, H?pital Cochin||H?pital Am¨|ricain de ParisUniversit¨| de Paris, Institut Cochin, CNRSUMR8104, INSERM U1016, A Member of OPALE Carnot Institute, The Organization for Partnerships in LeukemiaUniversit¨| de Paris, Institut Cochin, CNRSUMR8104, INSERM U1016, A Member of OPALE Carnot Institute, The Organization for Partnerships in LeukemiaAssistance Publique-H?pitaux de Paris, Centre-Universit¨| de Paris, Service d?ˉH¨|matologie Clinique, H?pital CochinUniversit¨| de Paris, Institut Cochin, CNRSUMR8104, INSERM U1016, A Member of OPALE Carnot Institute, The Organization for Partnerships in Leukemia||Assistance Publique-H?pitaux de Paris. Centre - Universit¨| de Paris, Service d?ˉH¨|matologie biologique, H?pital Cochin
基础医学细胞生物学分子生物学
Kosmider Olivier,Gaillard Mathilde,Zaroili Laila,Knosp Camille,Friedrich Chlo¨|,Asquier Philippe,Fontenay Michaela,Plesa Adriana,Gandrillon Olivier,Sujobert Pierre,Bouscary Didier,Espinasse Thibault,Quint Laurent,Boussaroque Agathe,Bravetti Clotilde,Willems Lise,Dussiau Charles.Hematopoietic differentiation is characterized by a transient peak of cell-to-cell gene expression variability in normal and pathological conditions[EB/OL].(2025-03-28)[2025-07-16].https://www.biorxiv.org/content/10.1101/2021.04.30.442092.点此复制
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