Pedone Elisa, Olteanu Vlad-Aris, Marucci Lucia, Muñoz-Martin Maria Isabel, Youssef Sameh A, de Bruin Alain, Cosma Maria Pia
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.
Department of Engineering Mathematics, University of Bristol, Bristol BS8 1UB, UK.
Cell Rep. 2017 Jan 3;18(1):107-121. doi: 10.1016/j.celrep.2016.12.008.
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.
在啮齿动物和人类中，肝脏在肝切除术后能够有效地恢复其质量。这在很大程度上归因于肝细胞的增殖和细胞周期重新进入。另一方面，骨髓细胞（BMCs）在切除术后会迁移到肝脏中。在这里，我们发现阻止BMCs募集到肝脏会严重损害其术后再生。切除的肝脏中动员的造血干细胞和祖细胞（HSPCs）可以与肝细胞融合，并且杂交细胞比肝细胞更早增殖。杂交细胞的基因消融严重损害肝细胞增殖和肝脏质量再生。数学模型揭示了骨髓（BM）来源的杂交细胞在驱动再生过程中增殖的关键作用，并预测了在实验不可测试条件下的再生效率。总之，BM来源的杂交细胞对于肝切除术后触发有效的肝脏再生至关重要。
