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

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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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

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

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10.1016/j.celrep.2016.12.008

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This is the final published version of the article (version of record). It first appeared online via Elsevier (Cell) at http://www.cell.com/cell-reports/abstract/S2211-1247(16)31681-3. Please refer to any applicable terms of use of the publisher.
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.
1/09/16 → 29/02/20
Project: Research

Dr Lucia Marucci
- lucia.maruccibristol.acuk
- School of Engineering Mathematics and Technology - Associate Professor in Systems and Synthetic Biology
Person: Academic

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 = "cell fusion, mathematical modeling, liver regeneration, partial hepatectomy, hematopoietic stem cells, cell migration, cell recruitment, 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",

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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 - cell fusion

KW - mathematical modeling

KW - liver regeneration

KW - partial hepatectomy

KW - hematopoietic stem cells

KW - cell migration

KW - cell recruitment

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

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Keywords

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Unravelling the role of beta-catenin in ground state pluripotency

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