Speicher Chris, Bergmann Monika, Brehm Klaus
Institute of Hygiene and Microbiology, University of Würzburg, Josef-Schneider-Strasse 2, 97080, Würzburg, Germany.
Parasitol Res. 2024 Dec 23;123(12):418. doi: 10.1007/s00436-024-08442-4.
Pluripotent somatic stem cells are the drivers of unlimited growth of Echinococcus multilocularis metacestode tissue within the organs of the intermediate host. To understand the dynamics of parasite proliferation within the host, it is therefore important to delineate basic mechanisms of Echinococcus stem cell maintenance and differentiation. We herein undertake the first step towards characterizing the role of an evolutionarily old metazoan cell-cell communication system, delta/notch signalling, in Echinococcus cell fate decisions. Bioinformatic analyses revealed that all central components of this pathway are encoded by the Echinococcus genome and are expressed in parasite larval stages. By in situ hybridisation, we analyzed the expression patterns of clearly identified delta-like ligands, delta1 and delta2, as well as two notch receptors, notch1 and notch2, in metacestode tissue. Except for delta1, which is not expressed in the metacestode, all other components are expressed in distinct cells throughout the parasite's germinal layer. Combined in situ hybridisation and EdU incorporation experiments together with pulse-chase assays further indicate that delta2, notch1, and notch2 are exclusively expressed in post-mitotic cells. Echinococcus asymmetric stem cell division, leading to the progeny of different fates, therefore most probably not involves delta/notch signalling components. Our analyses are relevant for understanding the interplay of fate-determining signalling pathways in Echinococcus cell differentiation and form a basis for further experiments into the role of delta/notch signalling in parasite development.
多能性体细胞干细胞是多房棘球绦虫中绦期组织在中间宿主器官内无限生长的驱动因素。因此,为了了解寄生虫在宿主体内增殖的动态过程,明确棘球绦虫干细胞维持和分化的基本机制至关重要。我们在此朝着阐明一种进化上古老的后生动物细胞间通讯系统——δ/Notch信号通路在棘球绦虫细胞命运决定中的作用迈出了第一步。生物信息学分析表明,该信号通路的所有核心组分均由棘球绦虫基因组编码,并在寄生虫幼虫阶段表达。通过原位杂交,我们分析了在中绦期组织中明确鉴定出的δ样配体delta1和delta2以及两种Notch受体Notch1和Notch2的表达模式。除了在中绦期不表达的delta1外,所有其他组分在整个寄生虫生发层的不同细胞中均有表达。原位杂交与EdU掺入实验以及脉冲追踪分析相结合进一步表明,delta2、Notch1和Notch2仅在有丝分裂后的细胞中表达。因此,棘球绦虫不对称干细胞分裂产生不同命运的子代,很可能不涉及δ/Notch信号通路组分。我们的分析对于理解棘球绦虫细胞分化中命运决定信号通路的相互作用具有重要意义,并为进一步研究δ/Notch信号通路在寄生虫发育中的作用奠定了基础。