Dynamic interplay between IL-1 and WNT pathways in regulating dermal adipocyte lineage cells during skin development and wound regeneration.
Dynamic interplay between IL-1 and WNT pathways in regulating dermal adipocyte lineage cells during skin development and wound regeneration.
复制标题
DOI：
10.1016/j.celrep.2023.112647
复制
发表时间：
2023-06-27
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
真皮脂肪细胞系细胞具有高度的可塑性，可以在各种刺激下进行可逆分化和去分化。利用发育中或损伤的小鼠皮肤的单细胞RNA测序，我们将真皮成纤维细胞分为不同的非成脂和成脂细胞状态。细胞分化轨迹分析表明，IL-1-NF-κB和WnT-β-Catenin分别是与脂肪形成正相关和负相关的顶级信号通路。在创伤后，脂肪细胞前体细胞的激活和创伤诱导的脂肪形成部分是由中性粒细胞通过IL-1R-NF-κB-CREB信号轴介导的。相反，通过WNT配体和/或去除GSK3激活WNT，抑制了dFBs的成脂潜力，但促进了成熟脂肪细胞的脂解和去分化，促进了肌成纤维细胞的形成。最后，在人类瘢痕疙瘩中可以看到WNT的持续激活和脂肪生成的抑制。这些数据揭示了真皮脂肪细胞系细胞可塑性的分子机制，为缺陷伤口愈合和疤痕形成确定了潜在的治疗靶点。真皮脂肪细胞系细胞是高度可塑性的细胞，可以对刺激做出反应而扩张或收缩。张和他的同事定义了这些细胞在发育或受伤的小鼠皮肤中的异质性，并证明了皮肤脂肪生成和脂肪分解是由IL-1-pCREB和WNT-β连环蛋白通路之间的拮抗相互作用调节的。
Dermal adipocyte lineage cells are highly plastic and can undergo reversible differentiation and dedifferentiation in response to various stimuli. Using single-cell RNA sequencing of developing or wounded mouse skin, we classify dermal fibroblasts (dFBs) into distinct non-adipogenic and adipogenic cell states. Cell differentiation trajectory analyses identify IL-1-NF-κB and WNT-β-catenin as top signaling pathways that positively and negatively associate with adipogenesis, respectively. Upon wounding, activation of adipocyte progenitors and wound-induced adipogenesis are mediated in part by neutrophils through the IL-1R-NF-κB-CREB signaling axis. In contrast, WNT activation, by WNT ligand and/or ablation of Gsk3, inhibits the adipogenic potential of dFBs but promotes lipolysis and dedifferentiation of mature adipocytes, contributing to myofibroblast formation. Finally, sustained WNT activation and inhibition of adipogenesis is seen in human keloids. These data reveal molecular mechanisms underlying the plasticity of dermal adipocyte lineage cells, defining potential therapeutic targets for defective wound healing and scar formation. Dermal adipocyte lineage cells are highly plastic cells that expand or retract in response to stimuli. Zhang and colleagues define the heterogeneity of these cells in developing or wounded mouse skin and demonstrate that dermal adipogenesis and lipolysis are regulated by an antagonistic interplay between the IL-1-pCREB and the WNT-β catenin pathways.
登录
查看更多内容
影响因子：
23.9
作者：
Joost, Simon;Annusver, Karl;Kasper, Maria
通讯作者：
Kasper, Maria
影响因子：
3.7
作者：
Morosan-Puopolo G;Balakrishnan-Renuka A;Yusuf F;Chen J;Dai F;Zoidl G;Lüdtke TH;Kispert A;Theiss C;Abdelsabour-Khalaf M;Brand-Saberi B
通讯作者：
Brand-Saberi B
影响因子：
4.6
作者：
Benias, Petros C.;Wells, Rebecca G.;Theise, Neil D.
通讯作者：
Theise, Neil D.
影响因子：
11.8
作者：
Doble, Bradley W.;Patel, Satish;Woodgett, James R.
通讯作者：
Woodgett, James R.
影响因子：
6
作者：
Haydont, Valerie;Neiveyans, Veronique;Fortunel, Nicolas O.
通讯作者：
Fortunel, Nicolas O.