小柯机器人

美国斯坦福大学Michael T. Longaker和Hunter B. Fraser研究组发现，等位基因特异性表达揭示了小鼠组织再生的遗传驱动因素。该项研究成果发表在近日出版的《细胞—干细胞》上。

在MRL和非再生小鼠的杂交杂交中，他们使用等位基因特异性基因表达来鉴定与耳部再生相关的顺式调控变异。通过分析三种主要的细胞群(免疫细胞、成纤维细胞和内皮细胞)，他们发现在成纤维细胞中具有顺式调控差异的基因与伤口愈合途径相关，并且与耳朵伤口愈合的数量性状位点共定位。补体因子H (CFH)是这些蛋白中的一种，异位治疗可加速典型纤维化伤口的修复和诱导再生。通过单细胞RNA测序(RNA-seq)，他们观察到CFH治疗显著减少了免疫细胞对伤口的募集，这提示了CFH作用的潜在机制。

总的来说，他们的结果提供了对再生的分子驱动因素的见解，具有潜在的临床意义。

据介绍，在成年哺乳动物中，皮肤伤口通常通过疤痕而不是再生来愈合。相比之下，“超级治疗者”墨菲罗斯大(MRL)小鼠具有不寻常的能力，可以使耳朵上的伤口再生;然而，这种再生的分子基础仍然难以捉摸。

附：英文原文

Title: Allele-specific expression reveals genetic drivers of tissue regeneration in mice

Author: Katya L. Mack, Heather E. Talbott, Michelle F. Griffin, Jennifer B.L. Parker, Nicholas J. Guardino, Amanda F. Spielman, Michael F. Davitt, Shamik Mascharak, Mauricio Downer, Annah Morgan, Caleb Valencia, Deena Akras, Mark J. Berger, Derrick C. Wan, Hunter B. Fraser, Michael T. Longaker

Issue&Volume:

Abstract: In adult mammals, skin wounds typically heal by scarring rather than through regeneration.In contrast, “super-healer” Murphy Roths Large (MRL) mice have the unusual abilityto regenerate ear punch wounds; however, the molecular basis for this regenerationremains elusive. Here, in hybrid crosses between MRL and non-regenerating mice, weused allele-specific gene expression to identify cis-regulatory variation associated with ear regeneration. Analyzing three major cellpopulations (immune, fibroblast, and endothelial), we found that genes with cis-regulatory differences specifically in fibroblasts were associated with wound-healingpathways and also co-localized with quantitative trait loci for ear wound-healing.Ectopic treatment with one of these proteins, complement factor H (CFH), acceleratedwound repair and induced regeneration in typically fibrotic wounds. Through single-cellRNA sequencing (RNA-seq), we observed that CFH treatment dramatically reduced immunecell recruitment to wounds, suggesting a potential mechanism for CFH’s effect. Overall,our results provide insights into the molecular drivers of regeneration with potentialclinical implications.

DOI: 10.1016/j.stem.2023.08.010

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00293-X

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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