Technische Universität Dresden, CRTD/Center for Regenerative Therapies Dresden, Dresden, Germany.
Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.
Nat Commun. 2022 Mar 3;13(1):1141. doi: 10.1038/s41467-022-28755-1.
Salamander limb regeneration is an accurate process which gives rise exclusively to the missing structures, irrespective of the amputation level. This suggests that cells in the stump have an awareness of their spatial location, a property termed positional identity. Little is known about how positional identity is encoded, in salamanders or other biological systems. Through single-cell RNAseq analysis, we identified Tig1/Rarres1 as a potential determinant of proximal identity. Tig1 encodes a conserved cell surface molecule, is regulated by retinoic acid and exhibits a graded expression along the proximo-distal axis of the limb. Its overexpression leads to regeneration defects in the distal elements and elicits proximal displacement of blastema cells, while its neutralisation blocks proximo-distal cell surface interactions. Critically, Tig1 reprogrammes distal cells to a proximal identity, upregulating Prod1 and inhibiting Hoxa13 and distal transcriptional networks. Thus, Tig1 is a central cell surface determinant of proximal identity in the salamander limb.
蝾螈肢体再生是一个精确的过程,它只产生缺失的结构,而与截肢水平无关。这表明残端中的细胞对其空间位置有一定的认识,这种特性被称为位置身份。目前对于蝾螈或其他生物系统中位置身份是如何编码的知之甚少。通过单细胞 RNAseq 分析,我们鉴定出 Tig1/Rarres1 是近端身份的一个潜在决定因素。Tig1 编码一种保守的细胞表面分子,受视黄酸调控,并沿肢体的近-远端轴呈梯度表达。它的过表达导致远端元素再生缺陷,并引发芽基细胞的近端移位,而其中和则阻止近-远端细胞表面相互作用。至关重要的是,Tig1 将远端细胞重新编程为近端身份,上调 Prod1 并抑制 Hoxa13 和远端转录网络。因此,Tig1 是蝾螈肢体中近端身份的核心细胞表面决定因素。