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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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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. |
format | Online Article Text |
id | pubmed-10285640 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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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