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A Temporary Pause in the Replication Licensing Restriction Leads to Rereplication during Early Human Cell Differentiation
Gene amplifications in amphibians and flies are known to occur during development and have been well characterized, unlike in mammalian cells, where they are predominantly investigated as an attribute of tumors. Recently, we first described gene amplifications in human and mouse neural stem cells, m...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946923/ https://www.ncbi.nlm.nih.gov/pubmed/35326512 http://dx.doi.org/10.3390/cells11061060 |
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author | Minet, Marie Abu-Halima, Masood Du, Yiqing Doerr, Julia Isted, Christina Ludwig, Nicole Keller, Andreas Meese, Eckart Fischer, Ulrike |
author_facet | Minet, Marie Abu-Halima, Masood Du, Yiqing Doerr, Julia Isted, Christina Ludwig, Nicole Keller, Andreas Meese, Eckart Fischer, Ulrike |
author_sort | Minet, Marie |
collection | PubMed |
description | Gene amplifications in amphibians and flies are known to occur during development and have been well characterized, unlike in mammalian cells, where they are predominantly investigated as an attribute of tumors. Recently, we first described gene amplifications in human and mouse neural stem cells, myoblasts, and mesenchymal stem cells during differentiation. The mechanism leading to gene amplifications in amphibians and flies depends on endocycles and multiple origin-firings. So far, there is no knowledge about a comparable mechanism in normal human cells. Here, we describe rereplication during the early myotube differentiation of human skeletal myoblast cells, using fiber combing and pulse-treatment with EdU (5′-Ethynyl-2′-deoxyuridine)/CldU (5-Chlor-2′-deoxyuridine) and IdU (5-Iodo-2′-deoxyuridine)/CldU. We found rereplication during a restricted time window between 2 h and 8 h after differentiation induction. Rereplication was detected in cells simultaneously with the amplification of the MDM2 gene. Our findings support rereplication as a mechanism enabling gene amplification in normal human cells. |
format | Online Article Text |
id | pubmed-8946923 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89469232022-03-25 A Temporary Pause in the Replication Licensing Restriction Leads to Rereplication during Early Human Cell Differentiation Minet, Marie Abu-Halima, Masood Du, Yiqing Doerr, Julia Isted, Christina Ludwig, Nicole Keller, Andreas Meese, Eckart Fischer, Ulrike Cells Article Gene amplifications in amphibians and flies are known to occur during development and have been well characterized, unlike in mammalian cells, where they are predominantly investigated as an attribute of tumors. Recently, we first described gene amplifications in human and mouse neural stem cells, myoblasts, and mesenchymal stem cells during differentiation. The mechanism leading to gene amplifications in amphibians and flies depends on endocycles and multiple origin-firings. So far, there is no knowledge about a comparable mechanism in normal human cells. Here, we describe rereplication during the early myotube differentiation of human skeletal myoblast cells, using fiber combing and pulse-treatment with EdU (5′-Ethynyl-2′-deoxyuridine)/CldU (5-Chlor-2′-deoxyuridine) and IdU (5-Iodo-2′-deoxyuridine)/CldU. We found rereplication during a restricted time window between 2 h and 8 h after differentiation induction. Rereplication was detected in cells simultaneously with the amplification of the MDM2 gene. Our findings support rereplication as a mechanism enabling gene amplification in normal human cells. MDPI 2022-03-21 /pmc/articles/PMC8946923/ /pubmed/35326512 http://dx.doi.org/10.3390/cells11061060 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Minet, Marie Abu-Halima, Masood Du, Yiqing Doerr, Julia Isted, Christina Ludwig, Nicole Keller, Andreas Meese, Eckart Fischer, Ulrike A Temporary Pause in the Replication Licensing Restriction Leads to Rereplication during Early Human Cell Differentiation |
title | A Temporary Pause in the Replication Licensing Restriction Leads to Rereplication during Early Human Cell Differentiation |
title_full | A Temporary Pause in the Replication Licensing Restriction Leads to Rereplication during Early Human Cell Differentiation |
title_fullStr | A Temporary Pause in the Replication Licensing Restriction Leads to Rereplication during Early Human Cell Differentiation |
title_full_unstemmed | A Temporary Pause in the Replication Licensing Restriction Leads to Rereplication during Early Human Cell Differentiation |
title_short | A Temporary Pause in the Replication Licensing Restriction Leads to Rereplication during Early Human Cell Differentiation |
title_sort | temporary pause in the replication licensing restriction leads to rereplication during early human cell differentiation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946923/ https://www.ncbi.nlm.nih.gov/pubmed/35326512 http://dx.doi.org/10.3390/cells11061060 |
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