title: Modeling Dynamics and Function of Bone Marrow Cells in Mouse Liver Regeneration.
abstract: In rodents and humans, the liver can efficiently restore its mass after hepatectomy. This is largely attributed to the proliferation and cell cycle re-entry of hepatocytes. On the other hand, bone marrow cells (BMCs) migrate into the liver after resection. Here, we find that a block of BMC recruitment into the liver severely impairs its regeneration after the surgery. Mobilized hematopoietic stem and progenitor cells (HSPCs) in the resected liver can fuse with hepatocytes, and the hybrids proliferate earlier than the hepatocytes. Genetic ablation of the hybrids severely impairs hepatocyte proliferation and liver mass regeneration. Mathematical modeling reveals a key role of bone marrow (BM)-derived hybrids to drive proliferation in the regeneration process, and predicts regeneration efficiency in experimentally non-testable conditions. In conclusion, BM-derived hybrids are essential to trigger efficient liver regeneration after hepatectomy.
authors.affiliation: Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr Aiguader 88, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Pedone
authors.affiliation: Department of Engineering Mathematics, University of Bristol, Bristol BS8 1UB, UK.
authors.forename: Vlad-Aris
authors.initials: VA
authors.lastname: Olteanu
authors.affiliation: Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr Aiguader 88, 08003 Barcelona, Spain; Department of Engineering Mathematics, University of Bristol, Bristol BS8 1UB, UK. Electronic address: lucia.marucci@bristol.ac.uk.
authors.forename: Lucia
authors.initials: L
authors.lastname: Marucci
authors.affiliation: Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Muñoz-Martin
authors.affiliation: Dutch Molecular Pathology Center, Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, 3584 Utrecht, the Netherlands; Department of Pathology, Alexandria Veterinary College, University of Alexandria-Egypt, 21612 Alexandria, Egypt.
authors.forename: Sameh A
authors.initials: SA
authors.lastname: Youssef
authors.affiliation: Dutch Molecular Pathology Center, Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, 3584 Utrecht, the Netherlands; University Medical Center Groningen, Department of Pediatrics, University of Groningen, 9713 Groningen, the Netherlands.
authors.forename: Alain
authors.initials: A
authors.lastname: de Bruin
authors.affiliation: Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr Aiguader 88, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain; ICREA, Pg. Lluís Companys 23, 08010 Barcelona, Spain. Electronic address: pia.cosma@crg.es.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Cosma
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism*; D002459:Cell Fusion; D049109:Cell Proliferation; D017353:Gene Deletion; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology; D008099:Liver / Q000502:physiology*; D008115:Liver Regeneration / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D010641:Phenotype; D019718:Receptors, CXCR4 / Q000378:metabolism
chemical_list: D019718:Receptors, CXCR4
keywords: cell fusion; cell migration; cell recruitment; hematopoietic stem cells; liver regeneration; mathematical modeling; partial hepatectomy; proliferation; systems biology