近期,国际学术权威刊物自然出版集团旗下子刊《Scientific Reports》杂志在线发表了中国科学院生物化学与细胞生物学研究所赵允研究组的最新研究成果 “Repression of Abd-B by Polycomb is critical for cell identity maintenance in adult Drosophila testis”。研究发现Hox基因Abd-B在Ploycomb(Pc)蛋白的调控下对果蝇精巢干细胞稳态以及细胞身份确定发挥着重要作用。博士生张硕为论文第一作者,赵允研究员为论文通讯作者。
果蝇精巢作为研究成体干细胞功能的重要模型,对发育生物学以及再生医学具有十分重要的意义。在前期筛选过程中,研究人员发现Hox基因Abd-B在果蝇精巢中呈现较强的抑制状态,这暗示着该基因的抑制可能对果蝇精巢稳态维持发挥着重要的作用。通过实验,研究人员证实Abd-B的去抑制自主性地影响了Cyst Stem Cell (CySC,成体干细胞)的正常分化,使得细胞分化与增殖的平衡被打破,细胞更加趋于增殖;Abd-B的去抑制化状态还非自主性地抑制了果蝇Germline Stem Cell (GSC,生殖细胞)的分化,导致早期生殖细胞的增殖,同时调控了生殖细胞细胞身份(Cell Identity)的维持。
Hox基因的维持通常由PcG蛋白调控,通过进一步的筛选,研究人员发现敲低表观遗传因子Polycomb(Pc),果蝇精巢表现出类似于Abd-B去抑制状态的表型,同时通过染色证明了Abd-B在Pc敲低的状态下明显上调;而遗传学上下游分析进一步证明Abd-B受到Pc的抑制,从而维持精巢稳态和细胞特性的确定。
原文摘要:Hox genes play a fundamental role in regulating animal development. However, less is known about their functions on homeostasis maintenance in adult stem cells. Here, we report that the repression of an important axial Hox gene, Abdominal-B(Abd-B), in cyst stem cells (CySCs) is essential for the homeostasis and cell identity maintenance in the adult Drosophila testis. Derepression of Abd-B in CySCs disrupts the proper self-renewal of both germline stem cells (GSCs) and CySCs, and leads to an excessive expansion of early stage somatic cells, which originate from both lineages. We further demonstrate that canonical Polycomb (Pc) and functional pathway of Polycomb group (PcG) proteins are responsible for maintaining the germline cell identity non-autonomously via repressing Abd-B in CySCs in the adult Drosophila testis.