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Predicting the number of lifetime divisions for hematopoietic stem cells from telomere length measurements

How many times does a typical hematopoietic stem cell (HSC) divide to maintain a daily production of over [Formula: see text] blood cells over a human lifetime? It has been predicted that relatively few, slowly dividing HSCs occupy the top of the hematopoietic hierarchy. However, tracking HSCs direc...

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Detalles Bibliográficos
Autores principales: Boyle, Cole, Lansdorp, Peter M., Edelstein-Keshet, Leah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10285640/
https://www.ncbi.nlm.nih.gov/pubmed/37360685
http://dx.doi.org/10.1016/j.isci.2023.107053
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author Boyle, Cole
Lansdorp, Peter M.
Edelstein-Keshet, Leah
author_facet Boyle, Cole
Lansdorp, Peter M.
Edelstein-Keshet, Leah
author_sort Boyle, Cole
collection PubMed
description How many times does a typical hematopoietic stem cell (HSC) divide to maintain a daily production of over [Formula: see text] blood cells over a human lifetime? It has been predicted that relatively few, slowly dividing HSCs occupy the top of the hematopoietic hierarchy. However, tracking HSCs directly is extremely challenging due to their rarity. Here, we utilize previously published data documenting the loss of telomeric DNA repeats in granulocytes, to draw inferences about HSC division rates, the timing of major changes in those rates, as well as lifetime division totals. Our method uses segmented regression to identify the best candidate representations of the telomere length data. Our method predicts that, on average, an HSC divides 56 times over an 85-year lifespan (with lower and upper bounds of 36 and 120, respectively), with half of these divisions during the first 24 years of life.
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spelling pubmed-102856402023-06-23 Predicting the number of lifetime divisions for hematopoietic stem cells from telomere length measurements Boyle, Cole Lansdorp, Peter M. Edelstein-Keshet, Leah iScience Article How many times does a typical hematopoietic stem cell (HSC) divide to maintain a daily production of over [Formula: see text] blood cells over a human lifetime? It has been predicted that relatively few, slowly dividing HSCs occupy the top of the hematopoietic hierarchy. However, tracking HSCs directly is extremely challenging due to their rarity. Here, we utilize previously published data documenting the loss of telomeric DNA repeats in granulocytes, to draw inferences about HSC division rates, the timing of major changes in those rates, as well as lifetime division totals. Our method uses segmented regression to identify the best candidate representations of the telomere length data. Our method predicts that, on average, an HSC divides 56 times over an 85-year lifespan (with lower and upper bounds of 36 and 120, respectively), with half of these divisions during the first 24 years of life. Elsevier 2023-06-08 /pmc/articles/PMC10285640/ /pubmed/37360685 http://dx.doi.org/10.1016/j.isci.2023.107053 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Boyle, Cole
Lansdorp, Peter M.
Edelstein-Keshet, Leah
Predicting the number of lifetime divisions for hematopoietic stem cells from telomere length measurements
title Predicting the number of lifetime divisions for hematopoietic stem cells from telomere length measurements
title_full Predicting the number of lifetime divisions for hematopoietic stem cells from telomere length measurements
title_fullStr Predicting the number of lifetime divisions for hematopoietic stem cells from telomere length measurements
title_full_unstemmed Predicting the number of lifetime divisions for hematopoietic stem cells from telomere length measurements
title_short Predicting the number of lifetime divisions for hematopoietic stem cells from telomere length measurements
title_sort predicting the number of lifetime divisions for hematopoietic stem cells from telomere length measurements
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10285640/
https://www.ncbi.nlm.nih.gov/pubmed/37360685
http://dx.doi.org/10.1016/j.isci.2023.107053
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