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小鼠创伤后纤维化中基质成纤维细胞的不同起源和区域依赖性贡献。

Distinct origin and region-dependent contribution of stromal fibroblasts to fibrosis following traumatic injury in mice.

机构信息

Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.

Center for Neuromusculoskeletal Restorative Medicine, Shatin, Hong Kong.

出版信息

Nat Neurosci. 2024 Jul;27(7):1285-1298. doi: 10.1038/s41593-024-01678-4. Epub 2024 Jun 7.

DOI:10.1038/s41593-024-01678-4
PMID:38849523
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11239523/
Abstract

Fibrotic scar tissue formation occurs in humans and mice. The fibrotic scar impairs tissue regeneration and functional recovery. However, the origin of scar-forming fibroblasts is unclear. Here, we show that stromal fibroblasts forming the fibrotic scar derive from two populations of perivascular cells after spinal cord injury (SCI) in adult mice of both sexes. We anatomically and transcriptionally identify the two cell populations as pericytes and perivascular fibroblasts. Fibroblasts and pericytes are enriched in the white and gray matter regions of the spinal cord, respectively. Both cell populations are recruited in response to SCI and inflammation. However, their contribution to fibrotic scar tissue depends on the location of the lesion. Upon injury, pericytes and perivascular fibroblasts become activated and transcriptionally converge on the generation of stromal myofibroblasts. Our results show that pericytes and perivascular fibroblasts contribute to the fibrotic scar in a region-dependent manner.

摘要

纤维化瘢痕组织形成存在于人类和小鼠中。纤维化瘢痕会损害组织再生和功能恢复。然而，瘢痕形成的成纤维细胞的起源尚不清楚。在这里，我们发现，在成年雄性和雌性小鼠的脊髓损伤（SCI）后，纤维化瘢痕形成的基质成纤维细胞来源于两种血管周细胞群体。我们通过解剖和转录学鉴定这两种细胞群体为周细胞和血管周围成纤维细胞。成纤维细胞和周细胞分别在脊髓的白质和灰质区域富集。这两种细胞群体均在 SCI 和炎症反应中被招募。然而，它们对纤维化瘢痕组织的贡献取决于损伤的位置。在损伤时，周细胞和血管周围成纤维细胞被激活，并在转录水平上趋于生成基质肌成纤维细胞。我们的结果表明，周细胞和血管周围成纤维细胞以区域依赖性的方式促进纤维化瘢痕的形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d61e/11239523/fc7202fd3f1e/41593_2024_1678_Fig9_ESM.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d61e/11239523/fa39f4b346c7/41593_2024_1678_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d61e/11239523/7d9b0c021e2a/41593_2024_1678_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d61e/11239523/a30230524de3/41593_2024_1678_Fig8_ESM.jpg
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