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Compartmental Architecture and Dynamics of Hematopoiesis
BACKGROUND: Blood cell formation is maintained by the replication of hematopoietic stem cells (HSC) that continuously feed downstream “compartments” where amplification and differentiation of cells occurs, giving rise to all blood lineages. Whereas HSC replicate slowly, committed cells replicate fas...
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2007
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828630/ https://www.ncbi.nlm.nih.gov/pubmed/17406669 http://dx.doi.org/10.1371/journal.pone.0000345 |
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author | Dingli, David Traulsen, Arne Pacheco, Jorge M. |
author_facet | Dingli, David Traulsen, Arne Pacheco, Jorge M. |
author_sort | Dingli, David |
collection | PubMed |
description | BACKGROUND: Blood cell formation is maintained by the replication of hematopoietic stem cells (HSC) that continuously feed downstream “compartments” where amplification and differentiation of cells occurs, giving rise to all blood lineages. Whereas HSC replicate slowly, committed cells replicate faster as they become more differentiated. METHODOLOGY/SIGNIFICANT FINDING: We propose a multi-compartment model of hematopoiesis, designed on the principle of cell flow conservation under stationary conditions. Cells lost from one compartment due to differentiation are replaced by cells from the upstream compartment. We assume that there is a constant relationship between cell input and output in each compartment and fix the single parameter of the model using data available for granulocyte maturation. We predict that ∼31 mitotic events separate the HSC from the mature cells observed in the circulation. Besides estimating the number of compartments, our model allows us to estimate the size of each compartment, the rate of cell replication within each compartment, the mean time a given cell type contributes to hematopoiesis, the amplification rate in each compartment, as well as the mean time separating stem-cell replication and mature blood-cell formation. CONCLUSIONS: Despite its simplicity, the model agrees with the limited in vivo data available and can make testable predictions. In particular, our prediction of the average lifetime of a PIG-A mutated clone agrees closely with the experimental results available for the PIG-A gene mutation in healthy adults. The present elucidation of the compartment structure and dynamics of hematopoiesis may prove insightful in further understanding a variety of hematopoietic disorders. |
format | Text |
id | pubmed-1828630 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-18286302007-04-04 Compartmental Architecture and Dynamics of Hematopoiesis Dingli, David Traulsen, Arne Pacheco, Jorge M. PLoS One Research Article BACKGROUND: Blood cell formation is maintained by the replication of hematopoietic stem cells (HSC) that continuously feed downstream “compartments” where amplification and differentiation of cells occurs, giving rise to all blood lineages. Whereas HSC replicate slowly, committed cells replicate faster as they become more differentiated. METHODOLOGY/SIGNIFICANT FINDING: We propose a multi-compartment model of hematopoiesis, designed on the principle of cell flow conservation under stationary conditions. Cells lost from one compartment due to differentiation are replaced by cells from the upstream compartment. We assume that there is a constant relationship between cell input and output in each compartment and fix the single parameter of the model using data available for granulocyte maturation. We predict that ∼31 mitotic events separate the HSC from the mature cells observed in the circulation. Besides estimating the number of compartments, our model allows us to estimate the size of each compartment, the rate of cell replication within each compartment, the mean time a given cell type contributes to hematopoiesis, the amplification rate in each compartment, as well as the mean time separating stem-cell replication and mature blood-cell formation. CONCLUSIONS: Despite its simplicity, the model agrees with the limited in vivo data available and can make testable predictions. In particular, our prediction of the average lifetime of a PIG-A mutated clone agrees closely with the experimental results available for the PIG-A gene mutation in healthy adults. The present elucidation of the compartment structure and dynamics of hematopoiesis may prove insightful in further understanding a variety of hematopoietic disorders. Public Library of Science 2007-04-04 /pmc/articles/PMC1828630/ /pubmed/17406669 http://dx.doi.org/10.1371/journal.pone.0000345 Text en Dingli et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Dingli, David Traulsen, Arne Pacheco, Jorge M. Compartmental Architecture and Dynamics of Hematopoiesis |
title | Compartmental Architecture and Dynamics of Hematopoiesis |
title_full | Compartmental Architecture and Dynamics of Hematopoiesis |
title_fullStr | Compartmental Architecture and Dynamics of Hematopoiesis |
title_full_unstemmed | Compartmental Architecture and Dynamics of Hematopoiesis |
title_short | Compartmental Architecture and Dynamics of Hematopoiesis |
title_sort | compartmental architecture and dynamics of hematopoiesis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828630/ https://www.ncbi.nlm.nih.gov/pubmed/17406669 http://dx.doi.org/10.1371/journal.pone.0000345 |
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