鉴定需要 LRP1 进行骨修复的 LRP1+CD13+ 人骨膜干细胞。

IF 6.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL JCI insight Pub Date : 2024-10-15 DOI:10.1172/jci.insight.173831
Youngjae Jeong, Lorenzo R Deveza, Laura Ortinau, Kevin Lei, John R Dawson, Dongsu Park
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引用次数: 0

摘要

人类骨膜骨骼干细胞(P-SSCs)对皮质骨的维护和修复至关重要。然而,它们在体内的身份、分子特征和特异性标记仍然未知。在这里,单细胞测序发现人类骨膜含有表达已知SSC标记物PDPN和PDGFRA的SSC集群。值得注意的是,人类P-SSCs(而非骨髓SSCs(BM-SSCs))选择性地表达了新发现的标记物LRP1和CD13。这些 LRP1+CD13+ 人 P-SSCs 是血管周围细胞,具有很高的骨软骨生成潜能,但脂肪生成潜能极低。移植到小鼠骨损伤处后,它们在体内保持了自我更新能力。对小鼠骨膜的单细胞分析进一步证实了 LRP1 和 CD13 在 Prx1+ P-SSCs 中的优先表达。当Lrp1在Prx1系细胞中被有条件地删除时,会导致严重的骨畸形、短雕像和骨膜缺损。相比之下,在损伤部位使用 LRP1 激动剂进行局部治疗可诱导 P-SSC 早期增殖和骨愈合。因此,人类和小鼠的骨膜含有独特的骨软骨干细胞亚群,这些P-SSCs表达特异性标志物LRP1和CD13,通过LRP1的调节机制增强P-SSC的功能和骨修复。
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Identification of LRP1+CD13+ human periosteal stem cells that require LRP1 for bone repair.

Human periosteal skeletal stem cells (P-SSCs) are critical for cortical bone maintenance and repair. However, their in vivo identity, molecular characteristics, and specific markers remain unknown. Here, single-cell sequencing revealed human periosteum contains SSC clusters expressing known SSC markers, PDPN and PDGFRA. Notably, human P-SSCs, but not bone marrow SSCs (BM-SSCs), selectively expressed newly identified markers, LRP1 and CD13. These LRP1+CD13+ human P-SSCs were perivascular cells with high osteochondrogenic but minimal adipogenic potential. Upon transplantation into bone injuries in mice, they preserved self-renewal capability in vivo. Single-cell analysis of mouse periosteum further supported the preferential expression of LRP1 and CD13 in Prx1+ P-SSCs. When Lrp1 was conditionally deleted in Prx1-lineage cells, it led to severe bone deformity, short statue, and periosteal defects. By contrast, local treatment with a LRP1 agonist at the injury sites induced early P-SSC proliferation and bone healing. Thus, human and mouse periosteum contains unique osteochondrogenic stem cell subsets, and these P-SSCs express specific markers, LRP1 and CD13, with regulatory mechanism through LRP1 that enhances P-SSC function and bone repair.

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来源期刊
JCI insight
JCI insight Medicine-General Medicine
CiteScore
13.70
自引率
1.20%
发文量
543
审稿时长
6 weeks
期刊介绍: JCI Insight is a Gold Open Access journal with a 2022 Impact Factor of 8.0. It publishes high-quality studies in various biomedical specialties, such as autoimmunity, gastroenterology, immunology, metabolism, nephrology, neuroscience, oncology, pulmonology, and vascular biology. The journal focuses on clinically relevant basic and translational research that contributes to the understanding of disease biology and treatment. JCI Insight is self-published by the American Society for Clinical Investigation (ASCI), a nonprofit honor organization of physician-scientists founded in 1908, and it helps fulfill the ASCI's mission to advance medical science through the publication of clinically relevant research reports.
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