Single-cell transcriptomic analysis of small and large wounds reveals the distinct spatial organization of regenerative fibroblasts.
Single-cell transcriptomic analysis of small and large wounds reveals the distinct spatial organization of regenerative fibroblasts.
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DOI：
10.1111/exd.14244
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发表时间：
2021-01
影响因子：
3.6
通讯作者：
Driskell RR
中科院分区：
文献类型：
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作者：
Phan QM;Sinha S;Biernaskie J;Driskell RR
创伤诱导的毛囊新生（WIHN）是研究创伤修复过程中毛囊再生的重要模型。然而，使大的伤口更再生的真皮的细胞和分子成分还没有完全了解。在这里，我们比较和对比最近发表的小疤痕伤口的scRNA-seq数据，希望阐明成纤维细胞谱系在WIHN中的作用。我们的分析揭示了在再生伤口条件下新鉴定的上伤口成纤维细胞的过度表达，其表达视黄酸结合蛋白Crapp 1。这种再生细胞类型与鼠乳头状成纤维细胞谱系具有相似的基因特征，这是支持毛囊形态发生和稳态所必需的。比较瘢痕形成和再生伤口的RNA速度分析揭示了朝向上部和下部伤口成纤维细胞的不同轨迹，并且上部群体与专门的毛乳头密切相关。我们还提供了分析和解释，以调和组织学谱系追踪与最近研究大型伤口的报告中scRNA-seq数据之间的不一致性。最后，我们进行了一个计算测试，以映射的空间位置上的伤口成纤维细胞在大伤口，这表明，上周边成纤维细胞可能海港相当于那些在中心的再生能力。总的来说，我们结合多个样本的scRNA-seq再分析表明，毛囊再生需要上部伤口成纤维细胞，并且在伤口再上皮化过程中，乳头状成纤维细胞可能从伤口周边迁移到中心。此外，该出版物的数据可在我们的可搜索网络资源https://skinregeneration.org/上获得。
Wound‐induced hair follicle neogenesis (WIHN) has been an important model to study hair follicle regeneration during wound repair. However, the cellular and molecular components of the dermis that make large wounds more regenerative are not fully understood. Here, we compare and contrast recently published scRNA‐seq data of small scarring wounds to wounds that regenerate in hope to elucidate the role of fibroblasts lineages in WIHN. Our analysis revealed an over‐representation of the newly identified upper wound fibroblasts in regenerative wound conditions, which express the retinoic acid binding protein Crabp1. This regenerative cell type shares a similar gene signature to the murine papillary fibroblast lineage, which are necessary to support hair follicle morphogenesis and homeostasis. RNA velocity analysis comparing scarring and regenerating wounds revealed the divergent trajectories towards upper and lower wound fibroblasts and that the upper populations were closely associated with the specialized dermal papilla. We also provide analyses and explanation reconciling the inconsistency between the histological lineage tracing and the scRNA‐seq data from recent reports investigating large wounds. Finally, we performed a computational test to map the spatial location of upper wound fibroblasts in large wounds which revealed that upper peripheral fibroblasts might harbour equivalent regenerative competence as those in the centre. Overall, our scRNA‐seq reanalysis combining multiple samples suggests that upper wound fibroblasts are required for hair follicle regeneration and that papillary fibroblasts may migrate from the wound periphery to the centre during wound re‐epithelialization. Moreover, data from this publication are made available on our searchable web resource: https://skinregeneration.org/.
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影响因子：
23.9
作者：
Joost, Simon;Annusver, Karl;Kasper, Maria
通讯作者：
Kasper, Maria
影响因子：
3
作者：
Kristianto, Jasmin;Johnson, Michael G.;Zastrow, Ryley K.;Radcliff, Abigail B.;Blank, Robert D.
通讯作者：
Blank, Robert D.
影响因子：
11.8
作者：
Shin, Wisoo;Rosin, Nicole L.;Biernaskie, Jeff
通讯作者：
Biernaskie, Jeff
影响因子：
64.8
作者：
La Manno G;Soldatov R;Zeisel A;Braun E;Hochgerner H;Petukhov V;Lidschreiber K;Kastriti ME;Lönnerberg P;Furlan A;Fan J;Borm LE;Liu Z;van Bruggen D;Guo J;He X;Barker R;Sundström E;Castelo-Branco G;Cramer P;Adameyko I;Linnarsson S;Kharchenko PV
通讯作者：
Kharchenko PV
影响因子：
64.8
作者：
通讯作者：
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