Distinct Fibroblast Lineages Give Rise to NG2+ Pericyte Populations in Mouse Skin Development and Repair.

Distinct Fibroblast Lineages Give Rise to NG2+ Pericyte Populations in Mouse Skin Development and Repair.
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DOI:
10.3389/fcell.2021.675080
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发表时间:
2021
影响因子:
5.5
通讯作者:
Watt FM
Watt FM
中科院分区:
生物学2区
文献类型:
--
作者:
Goss G;Rognoni E;Salameti V;Watt FM

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我们研究了粘附在血管基底膜上的Ng 2+血管周围细胞群的发育起源及其对伤口愈合的贡献。神经/神经胶质抗原2(Ng 2)标记发育中和成年小鼠背部皮肤中的大多数血管周细胞(70-80%),比其他周细胞标记物Tbx 18、Nestin和Pdgfrβ表达的比例更高。在成年小鼠背部皮肤中,Ng 2+血管周围细胞可以根据它们是否单独或联合表达Pdgfrα和Pdgfrβ或Pdgfr阴性而分为4个群体。谱系追踪表明,尽管胚胎和新生儿背部皮肤中的Ng 2+细胞有助于多种细胞类型,但它们不会引起真皮内的滤泡间成纤维细胞。皮肤发育过程中不同成纤维细胞群体的谱系追踪显示,乳头状成纤维细胞(Lrig 1+)在真皮上部产生Ng 2+血管周细胞,而真皮下部的Ng 2+血管周细胞主要来源于网状Dlk 1+成纤维细胞。在成年皮肤受伤后,Ng 2+真皮细胞仅产生Ng 2+血管相关细胞,并且不贡献于其他成纤维细胞谱系。Ng 2 + Pdgfrβ+血管周围群体的相对丰度在创伤和非创伤皮肤中相当,表明在全层皮肤修复期间维持血管周围异质性。根据再生血管的位置,在伤口床中,Ng 2+血管周围群体主要来源于Lrig 1+乳头状或Dlk 1+网状成纤维细胞谱系。我们得出结论,Ng 2+血管周围细胞代表了一个异质性谱系限制的人口,主要是从乳头状或网状成纤维细胞谱系在组织再生。
We have examined the developmental origins of Ng2+ perivascular cell populations that adhere to the basement membrane of blood vessels, and their contribution to wound healing. Neural/glial antigen 2 (Ng2) labeled most perivascular cells (70–80%) in developing and adult mouse back skin, a higher proportion than expressed by other pericyte markers Tbx18, Nestin and Pdgfrβ. In adult mouse back skin Ng2+ perivascular cells could be categorized into 4 populations based on whether they expressed Pdgfrα and Pdgfrβ individually or in combination or were Pdgfr-negative. Lineage tracing demonstrated that although Ng2+ cells in embryonic and neonatal back skin contributed to multiple cell types they did not give rise to interfollicular fibroblasts within the dermis. Lineage tracing of distinct fibroblast populations during skin development showed that papillary fibroblasts (Lrig1+) gave rise to Ng2+ perivascular cells in the upper dermis, whilst Ng2+ perivascular cells in the lower dermis were primarily derived from reticular Dlk1+ fibroblasts. Following wounding of adult skin, Ng2+ dermal cells only give rise to Ng2+ blood vessel associated cells and did not contribute to other fibroblast lineages. The relative abundance of Ng2+ Pdgfrβ+ perivascular populations was comparable in wounded and non-wounded skin, indicating that perivascular heterogeneity was maintained during full thickness skin repair. In the wound bed Ng2+ perivascular populations were primarily derived from Lrig1+ papillary or Dlk1+ reticular fibroblast lineages, according to the location of the regenerating blood vessels. We conclude that Ng2+ perivascular cells represent a heterogeneous lineage restricted population that is primarily recruited from the papillary or reticular fibroblast lineages during tissue regeneration.
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