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Arid4b alters cell cycle and cell death dynamics during mouse embryonic stem cell differentiation
Cell division and death play an important role in embryonic development. Cell specialization is accompanied with slow proliferation and quiescence. Cell death is important for morphogenesis. Gene expression changes during differentiation is coordinated by lineage-specific transcription factors and c...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Scientific and Technological Research Council of Turkey
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877710/ https://www.ncbi.nlm.nih.gov/pubmed/33597822 http://dx.doi.org/10.3906/biy-2009-6 |
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author | GÜVEN, Gözde TERZİ ÇİZMECİOĞLU, Nihal |
author_facet | GÜVEN, Gözde TERZİ ÇİZMECİOĞLU, Nihal |
author_sort | GÜVEN, Gözde |
collection | PubMed |
description | Cell division and death play an important role in embryonic development. Cell specialization is accompanied with slow proliferation and quiescence. Cell death is important for morphogenesis. Gene expression changes during differentiation is coordinated by lineage-specific transcription factors and chromatin factors. It is not yet fully understood how alterations in gene expression and cell cycle/death mechanisms are connected. We previously identified a chromatin protein Arid4b as a critical factor for meso/endoderm differentiation of mouse embryonic stem cells (mESCs). The differentiation defect of Arid4b-deficient mESCs might be due to misregulation of cell proliferation or death. Here, we identified a role for Arid4b in cell cycle rewiring at the onset of differentiation. Arid4b-deficient differentiating cells have less proliferative capacity and their cell cycle profile is more similar to mESC stage than the differentiating wild-type cells. We found no evidence of increased DNA damage or checkpoint activation. Our investigation of cell death mechanisms found no contribution from autophagy but revealed a slight increase in Caspase-3 activation implying early apoptosis in Arid4b-deficient differentiating cells. Taken together, our data suggest Arid4b regulates cell cycle alterations during exit from pluripotency. Future studies will be instrumental in understanding whether these changes directly contribute to Arid4b-dependent differentiation control. |
format | Online Article Text |
id | pubmed-7877710 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Scientific and Technological Research Council of Turkey |
record_format | MEDLINE/PubMed |
spelling | pubmed-78777102021-02-16 Arid4b alters cell cycle and cell death dynamics during mouse embryonic stem cell differentiation GÜVEN, Gözde TERZİ ÇİZMECİOĞLU, Nihal Turk J Biol Article Cell division and death play an important role in embryonic development. Cell specialization is accompanied with slow proliferation and quiescence. Cell death is important for morphogenesis. Gene expression changes during differentiation is coordinated by lineage-specific transcription factors and chromatin factors. It is not yet fully understood how alterations in gene expression and cell cycle/death mechanisms are connected. We previously identified a chromatin protein Arid4b as a critical factor for meso/endoderm differentiation of mouse embryonic stem cells (mESCs). The differentiation defect of Arid4b-deficient mESCs might be due to misregulation of cell proliferation or death. Here, we identified a role for Arid4b in cell cycle rewiring at the onset of differentiation. Arid4b-deficient differentiating cells have less proliferative capacity and their cell cycle profile is more similar to mESC stage than the differentiating wild-type cells. We found no evidence of increased DNA damage or checkpoint activation. Our investigation of cell death mechanisms found no contribution from autophagy but revealed a slight increase in Caspase-3 activation implying early apoptosis in Arid4b-deficient differentiating cells. Taken together, our data suggest Arid4b regulates cell cycle alterations during exit from pluripotency. Future studies will be instrumental in understanding whether these changes directly contribute to Arid4b-dependent differentiation control. The Scientific and Technological Research Council of Turkey 2021-02-09 /pmc/articles/PMC7877710/ /pubmed/33597822 http://dx.doi.org/10.3906/biy-2009-6 Text en Copyright © 2021 The Author(s) This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Article GÜVEN, Gözde TERZİ ÇİZMECİOĞLU, Nihal Arid4b alters cell cycle and cell death dynamics during mouse embryonic stem cell differentiation |
title | Arid4b alters cell cycle and cell death dynamics during mouse embryonic stem cell differentiation |
title_full | Arid4b alters cell cycle and cell death dynamics during mouse embryonic stem cell differentiation |
title_fullStr | Arid4b alters cell cycle and cell death dynamics during mouse embryonic stem cell differentiation |
title_full_unstemmed | Arid4b alters cell cycle and cell death dynamics during mouse embryonic stem cell differentiation |
title_short | Arid4b alters cell cycle and cell death dynamics during mouse embryonic stem cell differentiation |
title_sort | arid4b alters cell cycle and cell death dynamics during mouse embryonic stem cell differentiation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877710/ https://www.ncbi.nlm.nih.gov/pubmed/33597822 http://dx.doi.org/10.3906/biy-2009-6 |
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