BCR-ABL promotes hematopoietic stem and progenitor cell formation in embryonic stem cells.

Autor: Artus J; INSERM UMRS-1310, Paris Saclay University, Villejuif, France; Paris Saclay University, Faculty of Medicine, Kremlin-Bicêtre, France. Electronic address: jerome.artus@universite-paris-saclay.fr., Zenych A; INSERM UMRS-1310, Paris Saclay University, Villejuif, France., Simanic I; INSERM UMRS-1310, Paris Saclay University, Villejuif, France; ATIP/Avenir/INSERM UMRS-1310 Paris Saclay University, Villejuif, France., Desterke C; INSERM UMRS-1310, Paris Saclay University, Villejuif, France; Paris Saclay University, Faculty of Medicine, Kremlin-Bicêtre, France; INGESTEM National iPSC Infrastructure, Villejuif, France; CITHERA, Centre for IPSC Therapies, INSERM UMS-45, Paris Saclay University Genopole, Evry, France., Clay D; INSERM UMS-44, Paris Saclay University, Villejuif, France., Saïm S; INSERM UMRS-1310, Paris Saclay University, Villejuif, France., Ijjeh Y; INSERM UMRS-1310, Paris Saclay University, Villejuif, France; ATIP/Avenir/INSERM UMRS-1310 Paris Saclay University, Villejuif, France., de Souza LEB; INSERM UMRS-1310, Paris Saclay University, Villejuif, France; ATIP/Avenir/INSERM UMRS-1310 Paris Saclay University, Villejuif, France., Coignard S; INSERM UMRS-1310, Paris Saclay University, Villejuif, France; ATIP/Avenir/INSERM UMRS-1310 Paris Saclay University, Villejuif, France., Bennaceur-Griscelli A; INSERM UMRS-1310, Paris Saclay University, Villejuif, France; Paris Saclay University, Faculty of Medicine, Kremlin-Bicêtre, France; INGESTEM National iPSC Infrastructure, Villejuif, France; CITHERA, Centre for IPSC Therapies, INSERM UMS-45, Paris Saclay University Genopole, Evry, France; APHP Paris Saclay, Department of Hematology, Hôpital Bicêtre and Paul Brousse, Villejuif, France., Turhan AG; INSERM UMRS-1310, Paris Saclay University, Villejuif, France; Paris Saclay University, Faculty of Medicine, Kremlin-Bicêtre, France; INGESTEM National iPSC Infrastructure, Villejuif, France; CITHERA, Centre for IPSC Therapies, INSERM UMS-45, Paris Saclay University Genopole, Evry, France; APHP Paris Saclay, Department of Hematology, Hôpital Bicêtre and Paul Brousse, Villejuif, France., Foudi A; INSERM UMRS-1310, Paris Saclay University, Villejuif, France; Paris Saclay University, Faculty of Medicine, Kremlin-Bicêtre, France; ATIP/Avenir/INSERM UMRS-1310 Paris Saclay University, Villejuif, France. Electronic address: adlen.foudi@inserm.fr.
Jazyk: angličtina
Zdroj: Experimental hematology [Exp Hematol] 2023 Aug; Vol. 124, pp. 22-35.e3. Date of Electronic Publication: 2023 Jun 16.
DOI: 10.1016/j.exphem.2023.06.002
Abstrakt: Generating hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) has been a long-lasting quest in the field of hematopoiesis. Previous studies suggested that enforced expression of BCR-ABL, the unique oncogenic driver of chronic myelogeneous leukemia (CML), in embryonic stem cells (ESCs)-derived hematopoietic cells is sufficient to confer long-term in vivo repopulating potential. To precisely uncover the molecular events regulated by the tyrosine kinase activity of BCR-ABL1 (p210) during the course of hematopoietic differentiation, we engineered a Tet-ON inducible system to modulate its expression in murine ESCs (mESCs). We showed in unique site-directed knock-in ESC model that BCR-ABL expression tightly regulated by doxycycline (dox) controls the formation and the maintenance of immature hematopoietic progenitors. Interestingly, these progenitors can be expanded in vitro for several passages in the presence of dox. Our analysis of cell surface markers and transcriptome compared with wild-type fetal and adult HSCs unraveled a similar molecular signature. Long-term culture initiating cell (LTC-IC) assay confirmed their self-renewal capacities albeit with a differentiation bias toward erythroid and myeloid cells. Collectively, our novel Tet-ON system represents a unique in vitro model to shed lights on ESC-derived hematopoiesis, CML initiation, and maintenance.
Competing Interests: Conflict of Interest Disclosure The authors declare no competing financial interests.
(Copyright © 2023. Published by Elsevier Inc.)
Databáze: MEDLINE
Externí odkaz: