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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...

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Autores principales: Minet, Marie, Abu-Halima, Masood, Du, Yiqing, Doerr, Julia, Isted, Christina, Ludwig, Nicole, Keller, Andreas, Meese, Eckart, Fischer, Ulrike
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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