Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
Stowers Institute for Medical Research, Kansas City, MO 64110, USA; Howard Hughes Medical Institute, Kansas City, MO 64110, USA.
Cell. 2018 Jun 14;173(7):1593-1608.e20. doi: 10.1016/j.cell.2018.05.006.
Proliferating cells known as neoblasts include pluripotent stem cells (PSCs) that sustain tissue homeostasis and regeneration of lost body parts in planarians. However, the lack of markers to prospectively identify and isolate these adult PSCs has significantly hampered their characterization. We used single-cell RNA sequencing (scRNA-seq) and single-cell transplantation to address this long-standing issue. Large-scale scRNA-seq of sorted neoblasts unveiled a novel subtype of neoblast (Nb2) characterized by high levels of PIWI-1 mRNA and protein and marked by a conserved cell-surface protein-coding gene, tetraspanin 1 (tspan-1). tspan-1-positive cells survived sub-lethal irradiation, underwent clonal expansion to repopulate whole animals, and when purified with an anti-TSPAN-1 antibody, rescued the viability of lethally irradiated animals after single-cell transplantation. The first prospective isolation of an adult PSC bridges a conceptual dichotomy between functionally and molecularly defined neoblasts, shedding light on mechanisms governing in vivo pluripotency and a source of regeneration in animals. VIDEO ABSTRACT.
被称为成体干细胞（neoblasts）的增殖细胞包括多能干细胞（PSCs），这些细胞维持组织内稳态，并在扁形动物中再生失去的身体部位。然而，缺乏能够前瞻性识别和分离这些成年 PSCs 的标志物，极大地阻碍了对它们的特性研究。我们使用单细胞 RNA 测序（scRNA-seq）和单细胞移植来解决这个长期存在的问题。对分选的成体干细胞进行大规模 scRNA-seq 揭示了一种新型的成体干细胞亚群（Nb2），其特征是高水平的 PIWI-1 mRNA 和蛋白，并由一个保守的细胞表面蛋白编码基因，四跨膜蛋白 1（tspan-1）标记。tspan-1 阳性细胞能在亚致死剂量的辐射下存活，进行克隆性扩张以重新填充整个动物，并且当用抗 TSPAN-1 抗体进行纯化时，能在单细胞移植后挽救致死剂量辐射动物的存活能力。首次对成年 PSC 的前瞻性分离，弥合了功能上和分子上定义的成体干细胞之间的概念二分法，揭示了体内多能性的调控机制和动物再生的来源。视频摘要。
