Department of Biological Sciences, Graduate School of Science, University of Tokyo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Development. 2023 Aug 1;150(15). doi: 10.1242/dev.200467. Epub 2023 Jul 31.
Xenopus laevis tadpoles can regenerate whole tails after amputation. We have previously reported that interleukin 11 (il11) is required for tail regeneration. In this study, we have screened for genes that support tail regeneration under Il11 signaling in a certain cell type and have identified the previously uncharacterized genes Xetrov90002578m.L and Xetrov90002579m.S [referred to hereafter as regeneration factors expressed on myeloid.L (rfem.L) and rfem.S]. Knockdown (KD) of rfem.L and rfem.S causes defects of tail regeneration, indicating that rfem.L and/or rfem.S are required for tail regeneration. Single-cell RNA sequencing (scRNA-seq) revealed that rfem.L and rfem.S are expressed in a subset of leukocytes with a macrophage-like gene expression profile. KD of colony-stimulating factor 1 (csf1), which is essential for macrophage differentiation and survival, reduced rfem.L and rfem.S expression levels and the number of rfem.L- and rfem.S-expressing cells in the regeneration bud. Furthermore, forced expression of rfem.L under control of the mpeg1 promoter, which drives rfem.L in macrophage-like cells, rescues rfem.L and rfem.S KD-induced tail regeneration defects. Our findings suggest that rfem.L or rfem.S expression in macrophage-like cells is required for tail regeneration.
非洲爪蟾蝌蚪在截肢后可以再生整个尾巴。我们之前曾报道过白细胞介素 11(il11)是尾巴再生所必需的。在这项研究中,我们在 Il11 信号的特定细胞类型下筛选了支持尾巴再生的基因,并鉴定了以前未被表征的基因 Xetrov90002578m.L 和 Xetrov90002579m.S [以下简称髓样细胞表达的再生因子(rfem.L)和 rfem.S]。rfem.L 和 rfem.S 的敲低(KD)导致尾巴再生缺陷,表明 rfem.L 和/或 rfem.S 是尾巴再生所必需的。单细胞 RNA 测序(scRNA-seq)显示,rfem.L 和 rfem.S 在具有巨噬细胞样基因表达谱的白细胞亚群中表达。集落刺激因子 1(csf1)的 KD,其对于巨噬细胞分化和存活至关重要,降低了 rfem.L 和 rfem.S 的表达水平以及再生芽中表达 rfem.L 和 rfem.S 的细胞数量。此外,在 mpeg1 启动子的控制下强制表达 rfem.L,该启动子驱动巨噬细胞样细胞中的 rfem.L,挽救了 rfem.L 和 rfem.S KD 诱导的尾巴再生缺陷。我们的研究结果表明,巨噬细胞样细胞中 rfem.L 或 rfem.S 的表达是尾巴再生所必需的。