Vascular architecture regulates mesenchymal stromal cell heterogeneity via P53-PDGF signaling in the mouse incisor

IF 19.8 1区 医学 Q1 CELL & TISSUE ENGINEERING Cell stem cell Pub Date : 2024-05-03 DOI:10.1016/j.stem.2024.04.011
Tingwei Guo, Fei Pei, Mingyi Zhang, Takahiko Yamada, Jifan Feng, Junjun Jing, Thach-Vu Ho, Yang Chai
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Abstract

Mesenchymal stem cells (MSCs) reside in niches to maintain tissue homeostasis and contribute to repair and regeneration. Although the physiological functions of blood and lymphatic vasculature are well studied, their regulation of MSCs as niche components remains largely unknown. Using adult mouse incisors as a model, we uncover the role of Trp53 in regulating vascular composition through THBS2 to maintain mesenchymal tissue homeostasis. Loss of Trp53 in GLI1+ progeny increases arteries and decreases other vessel types. Platelet-derived growth factors from arteries deposit in the MSC region and interact with PDGFRA and PDGFRB. Significantly, PDGFRA+ and PDGFRB+ cells differentially contribute to defined cell lineages in the adult mouse incisor. Collectively, our results highlight Trp53’s importance in regulating the vascular niche for MSCs. They also shed light on how different arterial cells provide unique cues to regulate MSC subpopulations and maintain their heterogeneity. Furthermore, they provide mechanistic insight into MSC-vasculature crosstalk.

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血管结构通过 P53-PDGF 信号调节小鼠门齿间充质基质细胞的异质性
间充质干细胞(MSCs)驻留在龛位中,以维持组织稳态并促进修复和再生。虽然血液和淋巴管的生理功能已被深入研究,但它们对作为龛位成分的间充质干细胞的调控作用在很大程度上仍不为人所知。我们以成年小鼠门齿为模型,揭示了Trp53通过THBS2调节血管组成以维持间充质组织稳态的作用。GLI1+后代中的Trp53缺失会增加动脉,减少其他类型的血管。来自动脉的血小板衍生生长因子沉积在间充质组织区域,并与 PDGFRA 和 PDGFRB 相互作用。值得注意的是,PDGFRA+ 和 PDGFRB+ 细胞对成年小鼠门齿中确定的细胞系有不同的贡献。总之,我们的研究结果凸显了 Trp53 在调节间充质干细胞血管龛中的重要性。这些结果还揭示了不同的动脉细胞如何提供独特的线索来调节间充质干细胞亚群并保持其异质性。此外,它们还为间充质干细胞与血管的相互影响提供了机理上的启示。
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来源期刊
Cell stem cell
Cell stem cell 生物-细胞生物学
CiteScore
37.10
自引率
2.50%
发文量
151
审稿时长
42 days
期刊介绍: Cell Stem Cell is a comprehensive journal covering the entire spectrum of stem cell biology. It encompasses various topics, including embryonic stem cells, pluripotency, germline stem cells, tissue-specific stem cells, differentiation, epigenetics, genomics, cancer stem cells, stem cell niches, disease models, nuclear transfer technology, bioengineering, drug discovery, in vivo imaging, therapeutic applications, regenerative medicine, clinical insights, research policies, ethical considerations, and technical innovations. The journal welcomes studies from any model system providing insights into stem cell biology, with a focus on human stem cells. It publishes research reports of significant importance, along with review and analysis articles covering diverse aspects of stem cell research.
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