Ptip safeguards the epigenetic control of skeletal stem cell quiescence and potency in skeletogenesis
Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved..
Stem cells remain in a quiescent state for long-term maintenance and preservation of potency; this process requires fine-tuning regulatory mechanisms. In this study, we identified the epigenetic landscape along the developmental trajectory of skeletal stem cells (SSCs) in skeletogenesis governed by a key regulator, Ptip (also known as Paxip1, Pax interaction with transcription-activation domain protein-1). Our results showed that Ptip is required for maintaining the quiescence and potency of SSCs, and loss of Ptip in type II collagen (Col2)+ progenitors causes abnormal activation and differentiation of SSCs, impaired growth plate morphogenesis, and long bone dysplasia. We also found that Ptip suppressed the glycolysis of SSCs through downregulation of phosphoglycerate kinase 1 (Pgk1) by repressing histone H3K27ac at the promoter region. Notably, inhibition of glycolysis improved the function of SSCs despite Ptip deficiency. To the best of our knowledge, this is the first study to establish an epigenetic framework based on Ptip, which safeguards skeletal stem cell quiescence and potency through metabolic control. This framework is expected to improve SSC-based treatments of bone developmental disorders.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Science bulletin - (2024) vom: 29. Feb. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liang, Jianfei [VerfasserIn] |
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| Links: |
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| Themen: |
Bone development |
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| Anmerkungen: |
Date Revised 16.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.scib.2024.02.036 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369827481 |
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| 500 | |a published: Print-Electronic | ||
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| 520 | |a Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a Stem cells remain in a quiescent state for long-term maintenance and preservation of potency; this process requires fine-tuning regulatory mechanisms. In this study, we identified the epigenetic landscape along the developmental trajectory of skeletal stem cells (SSCs) in skeletogenesis governed by a key regulator, Ptip (also known as Paxip1, Pax interaction with transcription-activation domain protein-1). Our results showed that Ptip is required for maintaining the quiescence and potency of SSCs, and loss of Ptip in type II collagen (Col2)+ progenitors causes abnormal activation and differentiation of SSCs, impaired growth plate morphogenesis, and long bone dysplasia. We also found that Ptip suppressed the glycolysis of SSCs through downregulation of phosphoglycerate kinase 1 (Pgk1) by repressing histone H3K27ac at the promoter region. Notably, inhibition of glycolysis improved the function of SSCs despite Ptip deficiency. To the best of our knowledge, this is the first study to establish an epigenetic framework based on Ptip, which safeguards skeletal stem cell quiescence and potency through metabolic control. This framework is expected to improve SSC-based treatments of bone developmental disorders | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Bone development | |
| 650 | 4 | |a Epigenetics | |
| 650 | 4 | |a Glycolysis | |
| 650 | 4 | |a Ptip | |
| 650 | 4 | |a Skeletal stem cells | |
| 700 | 1 | |a Wang, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Sui, Bingdong |e verfasserin |4 aut | |
| 700 | 1 | |a Tong, Yibo |e verfasserin |4 aut | |
| 700 | 1 | |a Chai, Jihua |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Qin |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Chenxi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Kong, Liang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Haojian |e verfasserin |4 aut | |
| 700 | 1 | |a Bai, Yi |e verfasserin |4 aut | |
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