Élisabeth Remy1, Estelle Duprez2, Léonard Hérault3,1, Mathilde Poplineau3, Adrien Mazuel3, Nadine Platet3. 1. Aix Marseille Université, CNRS, Centrale Marseille, I2M, Marseille, France. 2. Epigenetic Factors in Normal and Malignant Hematopoiesis Team, Aix Marseille Université, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Marseille, France. estelle.duprez@inserm.fr. 3. Epigenetic Factors in Normal and Malignant Hematopoiesis Team, Aix Marseille Université, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Marseille, France.
Abstract
BACKGROUND: Hematopoietic stem cells (HSCs) are the guarantor of the proper functioning of hematopoiesis due to their incredible diversity of potential. During aging, heterogeneity of HSCs changes, contributing to the deterioration of the immune system. In this study, we revisited mouse HSC compartment and its transcriptional plasticity during aging at unicellular scale. RESULTS: Through the analysis of 15,000 young and aged transcriptomes, we identified 15 groups of HSCs revealing rare and new specific HSC abilities that change with age. The implantation of new trajectories complemented with the analysis of transcription factor activities pointed consecutive states of HSC differentiation that were delayed by aging and explained the bias in differentiation of older HSCs. Moreover, reassigning cell cycle phases for each HSC clearly highlighted an imbalance of the cell cycle regulators of very immature aged HSCs that may contribute to their accumulation in an undifferentiated state. CONCLUSIONS: Our results establish a new reference map of HSC differentiation in young and aged mice and reveal a potential mechanism that delays the differentiation of aged HSCs and could promote the emergence of age-related hematologic diseases.
BACKGROUND: Hematopoietic stem cells (HSCs) are the guarantor of the proper functioning of hematopoiesis due to their incredible diversity of potential. During aging, heterogeneity of HSCs changes, contributing to the deterioration of the immune system. In this study, we revisited mouse HSC compartment and its transcriptional plasticity during aging at unicellular scale. RESULTS: Through the analysis of 15,000 young and aged transcriptomes, we identified 15 groups of HSCs revealing rare and new specific HSC abilities that change with age. The implantation of new trajectories complemented with the analysis of transcription factor activities pointed consecutive states of HSC differentiation that were delayed by aging and explained the bias in differentiation of older HSCs. Moreover, reassigning cell cycle phases for each HSC clearly highlighted an imbalance of the cell cycle regulators of very immature aged HSCs that may contribute to their accumulation in an undifferentiated state. CONCLUSIONS: Our results establish a new reference map of HSC differentiation in young and aged mice and reveal a potential mechanism that delays the differentiation of aged HSCs and could promote the emergence of age-related hematologic diseases.
Authors: Jörgen Adolfsson; Robert Månsson; Natalija Buza-Vidas; Anne Hultquist; Karina Liuba; Christina T Jensen; David Bryder; Liping Yang; Ole-Johan Borge; Lina A M Thoren; Kristina Anderson; Ewa Sitnicka; Yutaka Sasaki; Mikael Sigvardsson; Sten Eirik W Jacobsen Journal: Cell Date: 2005-04-22 Impact factor: 41.582
Authors: Alejo E Rodriguez-Fraticelli; Samuel L Wolock; Caleb S Weinreb; Riccardo Panero; Sachin H Patel; Maja Jankovic; Jianlong Sun; Raffaele A Calogero; Allon M Klein; Fernando D Camargo Journal: Nature Date: 2018-01-03 Impact factor: 49.962