Modelling dynamics and function of bone marrow cells in mouse liver regeneration

Elisa Pedone, Aris Olteanu, Lucia Marucci, Maria Isabel Munoz-Martin, Sameh A. Youssef, Alain de Bruin, MP Cosma

Research output: Contribution to journalArticle (Academic Journal)peer-review

14 Citations (Scopus)
278 Downloads (Pure)

Abstract

In rodents and humans the liver can restore its mass after hepatectomy efficiently. 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 modelling reveals a key role of BM-derived hybrids to drive proliferation in the regeneration process, and predicts regeneration efficiency in experimentally nontestable conditions. In conclusion, BM-derived hybrids are essential to trigger efficient liver regeneration after hepatectomy.
Original languageEnglish
Pages (from-to)107-121
Number of pages15
JournalCell Reports
Volume18
Issue number1
DOIs
Publication statusPublished - 3 Jan 2017

Bibliographical note

Accepted 1 Dec 2016

Structured keywords

  • BrisSynBio
  • Bristol BioDesign Institute

Keywords

  • cell fusion
  • mathematical modeling
  • liver regeneration
  • partial hepatectomy
  • hematopoietic stem cells
  • cell migration
  • cell recruitment
  • proliferation
  • systems biology

Fingerprint Dive into the research topics of 'Modelling dynamics and function of bone marrow cells in mouse liver regeneration'. Together they form a unique fingerprint.

Cite this