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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...

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Autores principales: Sorimachi, Yuriko, Kobayashi, Hiroshi, Shiozawa, Yusuke, Koide, Shuhei, Nakato, Ryuichiro, Shimizu, Yukiko, Okamura, Tadashi, Shirahige, Katsuhiko, Iwama, Atsushi, Goda, Nobuhito, Takubo, Kaiyo, Takubo, Keiyo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
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.
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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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