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Mesenchymal loss of p53 alters stem cell capacity and models human soft tissue sarcoma traits
Soft tissue sarcomas (STSs) are a heterogeneous group of tumors that originate from mesenchymal cells. p53 is frequently mutated in human STS. In this study, we found that the loss of p53 in mesenchymal stem cells (MSCs) mainly causes adult undifferentiated soft tissue sarcoma (USTS). MSCs lacking p...
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/PMC10202654/ https://www.ncbi.nlm.nih.gov/pubmed/37059101 http://dx.doi.org/10.1016/j.stemcr.2023.03.009 |
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author | Sorimachi, Yuriko Kobayashi, Hiroshi Shiozawa, Yusuke Koide, Shuhei Nakato, Ryuichiro Shimizu, Yukiko Okamura, Tadashi Shirahige, Katsuhiko Iwama, Atsushi Goda, Nobuhito Takubo, Kaiyo Takubo, Keiyo |
author_facet | Sorimachi, Yuriko Kobayashi, Hiroshi Shiozawa, Yusuke Koide, Shuhei Nakato, Ryuichiro Shimizu, Yukiko Okamura, Tadashi Shirahige, Katsuhiko Iwama, Atsushi Goda, Nobuhito Takubo, Kaiyo Takubo, Keiyo |
author_sort | Sorimachi, Yuriko |
collection | PubMed |
description | Soft tissue sarcomas (STSs) are a heterogeneous group of tumors that originate from mesenchymal cells. p53 is frequently mutated in human STS. In this study, we found that the loss of p53 in mesenchymal stem cells (MSCs) mainly causes adult undifferentiated soft tissue sarcoma (USTS). MSCs lacking p53 show changes in stem cell properties, including differentiation, cell cycle progression, and metabolism. The transcriptomic changes and genetic mutations in murine p53-deficient USTS mimic those seen in human STS. Furthermore, single-cell RNA sequencing revealed that MSCs undergo transcriptomic alterations with aging—a risk factor for certain types of USTS—and that p53 signaling decreases simultaneously. Moreover, we found that human STS can be transcriptomically classified into six clusters with different prognoses, different from the current histopathological classification. This study paves the way for understanding MSC-mediated tumorigenesis and provides an efficient mouse model for sarcoma studies. |
format | Online Article Text |
id | pubmed-10202654 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-102026542023-05-23 Mesenchymal loss of p53 alters stem cell capacity and models human soft tissue sarcoma traits Sorimachi, Yuriko Kobayashi, Hiroshi Shiozawa, Yusuke Koide, Shuhei Nakato, Ryuichiro Shimizu, Yukiko Okamura, Tadashi Shirahige, Katsuhiko Iwama, Atsushi Goda, Nobuhito Takubo, Kaiyo Takubo, Keiyo Stem Cell Reports Article Soft tissue sarcomas (STSs) are a heterogeneous group of tumors that originate from mesenchymal cells. p53 is frequently mutated in human STS. In this study, we found that the loss of p53 in mesenchymal stem cells (MSCs) mainly causes adult undifferentiated soft tissue sarcoma (USTS). MSCs lacking p53 show changes in stem cell properties, including differentiation, cell cycle progression, and metabolism. The transcriptomic changes and genetic mutations in murine p53-deficient USTS mimic those seen in human STS. Furthermore, single-cell RNA sequencing revealed that MSCs undergo transcriptomic alterations with aging—a risk factor for certain types of USTS—and that p53 signaling decreases simultaneously. Moreover, we found that human STS can be transcriptomically classified into six clusters with different prognoses, different from the current histopathological classification. This study paves the way for understanding MSC-mediated tumorigenesis and provides an efficient mouse model for sarcoma studies. Elsevier 2023-04-13 /pmc/articles/PMC10202654/ /pubmed/37059101 http://dx.doi.org/10.1016/j.stemcr.2023.03.009 Text en © 2023 The Author(s) 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 Sorimachi, Yuriko Kobayashi, Hiroshi Shiozawa, Yusuke Koide, Shuhei Nakato, Ryuichiro Shimizu, Yukiko Okamura, Tadashi Shirahige, Katsuhiko Iwama, Atsushi Goda, Nobuhito Takubo, Kaiyo Takubo, Keiyo Mesenchymal loss of p53 alters stem cell capacity and models human soft tissue sarcoma traits |
title | Mesenchymal loss of p53 alters stem cell capacity and models human soft tissue sarcoma traits |
title_full | Mesenchymal loss of p53 alters stem cell capacity and models human soft tissue sarcoma traits |
title_fullStr | Mesenchymal loss of p53 alters stem cell capacity and models human soft tissue sarcoma traits |
title_full_unstemmed | Mesenchymal loss of p53 alters stem cell capacity and models human soft tissue sarcoma traits |
title_short | Mesenchymal loss of p53 alters stem cell capacity and models human soft tissue sarcoma traits |
title_sort | mesenchymal loss of p53 alters stem cell capacity and models human soft tissue sarcoma traits |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10202654/ https://www.ncbi.nlm.nih.gov/pubmed/37059101 http://dx.doi.org/10.1016/j.stemcr.2023.03.009 |
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