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

doi:10.1016/j.celrep.2016.12.008

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

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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 language	English
Pages (from-to)	107-121
Number of pages	15
Journal	Cell Reports
Volume	18
Issue number	1
DOIs	https://doi.org/10.1016/j.celrep.2016.12.008
Publication status	Published - 3 Jan 2017

Bibliographical note

Accepted 1 Dec 2016

Research Groups and Themes

BrisSynBio
Bristol BioDesign Institute

Keywords

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

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10.1016/j.celrep.2016.12.008

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Final published version, 4 MBLicence: CC BY-NC-ND

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Unravelling the role of beta-catenin in ground state pluripotency
Marucci, L. (Principal Investigator)
1/09/16 → 29/02/20
Project: Research

Professor Lucia Marucci
- lucia.maruccibristol.acuk
- School of Engineering Mathematics and Technology - Professor of Systems and Engineering Biology
- Cancer
Person: Academic , Member

Cite this

@article{ed0f58f1cdfc42ada2a6e99fa4886092,

title = "Modelling dynamics and function of bone marrow cells in mouse liver regeneration",

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.",

keywords = "synthetic biology, cell fusion, partial hepatectomy, hematopoietic stem cells, liver regeneration, mathematical modeling, cell recruitment, cell migration, proliferation, systems biology",

author = "Elisa Pedone and Aris Olteanu and Lucia Marucci and Munoz-Martin, {Maria Isabel} and Youssef, {Sameh A.} and {de Bruin}, Alain and MP Cosma",

note = "Accepted 1 Dec 2016",

year = "2017",

month = jan,

day = "3",

doi = "10.1016/j.celrep.2016.12.008",

language = "English",

volume = "18",

pages = "107--121",

journal = "Cell Reports",

issn = "2211-1247",

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TY - JOUR

T1 - Modelling dynamics and function of bone marrow cells in mouse liver regeneration

AU - Pedone, Elisa

AU - Olteanu, Aris

AU - Marucci, Lucia

AU - Munoz-Martin, Maria Isabel

AU - Youssef, Sameh A.

AU - de Bruin, Alain

AU - Cosma, MP

N1 - Accepted 1 Dec 2016

PY - 2017/1/3

Y1 - 2017/1/3

N2 - 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.

AB - 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.

KW - synthetic biology

KW - cell fusion

KW - partial hepatectomy

KW - hematopoietic stem cells

KW - liver regeneration

KW - mathematical modeling

KW - cell recruitment

KW - cell migration

KW - proliferation

KW - systems biology

U2 - 10.1016/j.celrep.2016.12.008

DO - 10.1016/j.celrep.2016.12.008

M3 - Article (Academic Journal)

C2 - 28052241

SN - 2211-1247

VL - 18

SP - 107

EP - 121

JO - Cell Reports

JF - Cell Reports

IS - 1

ER -

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

Abstract

Bibliographical note

Research Groups and Themes

Keywords

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Projects

Unravelling the role of beta-catenin in ground state pluripotency

Profiles

Professor Lucia Marucci

Cite this