Identification of EmSOX2, a member of the Sox family of transcription factors, as a potential regulator of Echinococcus multilocularis germinative cells

Cheng, Zhe; Liu, Fan; Dai, Mengya; Wu, Jian‐Jian; Li, Xiu; Guo, Xinrui; Tian, Huimin; Heng, Zhijie; Lü, Ying; Chai, Xiaoli; Wang, Yanhai

doi:10.1016/j.ijpara.2017.03.005

Cited by 8 publications

(9 citation statements)

References 37 publications

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“…To achieve maximum depletion of stem cells prior to transcriptome analyses we performed metacestode vesicle treatment for 7 days with HU and for 21 days with Bi-2536, which most likely exceeds the average cell cycle duration of GC in metacestode vesicles ( Koziol et al., 2014 ; Cheng et al., 2017a ). It is thus possible that our list of GC associated factors also contains genes that are not expressed in GC, but in GC progeny already committed to a specific cell fate.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, only few markers have been identified that are strongly associated with GC. Apart from GC markers deriving from mobile genetic elements ( Koziol et al., 2015 ), the most important ones regarding stem cell regulation are the post-transcriptional regulators em-nos-1 and em-nos-2 , which are homologous to the general stem cell marker nanos (both are expressed in small sub-populations of GC; Koziol et al., 2014 ), as well as the transcriptional regulator EmSox2, which is related to human Sox2 ( Cheng et al., 2017a ). No data are presently available on GC gene regulatory networks governing maintenance of pluripotency, which is mostly due to a lack of information on stem cell-specific genes in Echinococcus .…”

Section: Introductionmentioning

confidence: 99%

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Genome-wide transcriptome analysis of Echinococcus multilocularis larvae and germinative cell cultures reveals genes involved in parasite stem cell function

Herz,

Zarowiecki,

Wessels

et al. 2024

Front. Cell. Infect. Microbiol.

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The lethal zoonosis alveolar echinococcosis is caused by tumour-like growth of the metacestode stage of the tapeworm Echinococcus multilocularis within host organs. We previously demonstrated that metacestode proliferation is exclusively driven by somatic stem cells (germinative cells), which are the only mitotically active parasite cells that give rise to all differentiated cell types. The Echinococcus gene repertoire required for germinative cell maintenance and differentiation has not been characterised so far. We herein carried out Illumina sequencing on cDNA from Echinococcus metacestode vesicles, from metacestode tissue depleted of germinative cells, and from Echinococcus primary cell cultures. We identified a set of ~1,180 genes associated with germinative cells, which contained numerous known stem cell markers alongside genes involved in replication, cell cycle regulation, mitosis, meiosis, epigenetic modification, and nucleotide metabolism. Interestingly, we also identified 44 stem cell associated transcription factors that are likely involved in regulating germinative cell differentiation and/or pluripotency. By in situ hybridization and pulse-chase experiments, we also found a new general Echinococcus stem cell marker, EmCIP2Ah, and we provide evidence implying the presence of a slow cycling stem cell sub-population expressing the extracellular matrix factor Emkal1. RNA-Seq analyses on primary cell cultures revealed that metacestode-derived Echinococcus stem cells display an expanded differentiation capability and do not only form differentiated cell types of the metacestode, but also cells expressing genes specific for protoscoleces, adult worms, and oncospheres, including an ortholog of the schistosome praziquantel target, EmTRPMPZQ. Finally, we show that primary cell cultures contain a cell population expressing an ortholog of the tumour necrosis factor α receptor family and that mammalian TNFα accelerates the development of metacestode vesicles from germinative cells. Taken together, our analyses provide a robust and comprehensive characterization of the Echinococcus germinative cell transcriptome, demonstrate expanded differentiation capability of metacestode derived stem cells, and underscore the potential of primary germinative cell cultures to investigate developmental processes of the parasite. These data are relevant for studies into the role of Echinococcus stem cells in parasite development and will facilitate the design of anti-parasitic drugs that specifically act on the parasite germinative cell compartment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genome-wide transcriptome analysis of Echinococcus multilocularis larvae and germinative cell cultures reveals genes involved in parasite stem cell function

Herz,

Zarowiecki,

Wessels

et al. 2024

Front. Cell. Infect. Microbiol.

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“…This is also surprising, since soxB homologs usually are expressed during the early specification of the neuroectoderm in animal embryos (Hartenstein and Stollewerk, 2015), although later roles during neuronal differentiation have also been described for particular soxB homologs (Guth and Wegner, 2008;Phochanukul and Russell, 2010;Monjo and Romero, 2015;Vidal et al, 2015). Furthermore, the ortholog of soxB in E. multilocularis is expressed in most proliferating germinative cells in the metacestode germinative layer (Cheng et al, 2017), which are unlikely to be neural precursors given the minimal nervous system present in this tissue (Koziol et al, 2013). Finally, tapeworms appear to lack many conserved regulators of neural development, such as neurogenin and elav (Montagne and 16 Koziol, unpublished data), hinting at a highly modified neurogenic program.…”

Section: Discussionmentioning

confidence: 99%

Stem cell proliferation and differentiation during larval metamorphosis of the model tapewormHymenolepis microstoma

Montagne,

Preza,

Koziol

2023

Preprint

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Tapeworm larvae cause important diseases in humans and domestic animals. During infection, the first larval stage undergoes a metamorphosis where tissues are formedde novofrom a population of stem cells called germinative cells. This process is difficult to study for human pathogens, as these larvae are infectious and difficult to maintain in the laboratory. In this work, we analyzed cell proliferation and differentiation during larval metamorphosis in the model tapewormHymenolepis microstoma, byin vivolabelling of proliferating cells with the thymidine analogue 5-ethynyl-2′-deoxyuridine (EdU), tracing their differentiation with a suite of specific molecular markers for different cell types. Proliferating cells are very abundant and fast-cycling during early metamorphosis: the total number of cells duplicates every ten hours, and the length of G2 is only 75 minutes. New tegumental, muscle and nerve cells differentiate from this pool of proliferating germinative cells, and these processes are very fast, as differentiation markers for neurons and muscle cells appear within 24 hours after exiting the cell cycle, and fusion of new cells to the tegumental syncytium can be detected after only 4 hours. Tegumental and muscle cells appear from early stages of metamorphosis (24 to 48 hours post-infection); in contrast, most markers for differentiating neurons appear later, and the detection of synapsin and neuropeptides correlates with scolex retraction. Finally, we identified populations of proliferating cells that express conserved genes associated with neuronal progenitors and precursors, suggesting the existence of tissue-specific lineages among germinative cells. These results provide for the first time a comprehensive view of the development of new tissues during tapeworm larval metamorphosis, providing a framework for similar studies in human and veterinary pathogens.

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“…Gene-expression analyses of cestode germinative cells are more recent and include the study of homologous genes of planarian neoblast markers in Echinococcus multilocularis (Em-nos-1, Em-nos-2, Em-ago-2, Em-h2b, Em-sox2, Em-fgfr3), as well as a transcriptomic study of irradiated Hymenolepis diminuta (Koziol et al, 2014(Koziol et al, , 2015Cheng et al, 2017;Förster et al, 2019;Rozario et al, 2019). Genomic analyses have shown that trematodes and cestodes have lost important germline multipotency programme (GMP) components, such as P-element Induced WImpy testis (PIWI), VASA and group 9 TUDOR proteins (Tsai et al, 2013;Fontenla et al, 2017Fontenla et al, , 2021.…”

Section: Introductionmentioning

confidence: 99%

Cell repertoire and proliferation of germinative cells of the model cestode Mesocestoides corti

et al. 2022

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The phylum Platyhelminthes shares a unique population of undifferentiated cells responsible for the proliferation capacity needed for cell renewal, growth, tissue repair and regeneration. These cells have been extensively studied in free-living flatworms, whereas in cestodes the presence of a set of undifferentiated cells, known as germinative cells, has been demonstrated in classical morphology studies, but poorly characterized with molecular biology approaches. Furthermore, several genes have been identified as neoblast markers in free-living flatworms that deserve study in cestode models. Here, different cell types of the model cestode Mesocestoides corti were characterized, identifying differentiated and germinative cells. Muscle cells, tegumental cells, calcareous corpuscle precursor cells and excretory system cells were identified, all of which are non-proliferative, differentiated cell types. Besides those, germinative cells were identified as a population of small cells with proliferative capacity in vivo. Primary cell culture experiments in Dulbecco's Modified Eagle Medium (DMEM), Echinococcus hydatid fluid and hepatocyte conditioned media in non-reductive or reductive conditions confirmed that the germinative cells were the only ones with proliferative capacity. Since several genes have been identified as markers of undifferentiated neoblast cells in free-living flatworms, the expression of pumilio and pL10 genes was analysed by qPCR and in situ hybridization, showing that the expression of these genes was stronger in germinative cells but not restricted to this cell type. This study provides the first tools to analyse and further characterise undifferentiated cells in a model cestode.

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Identification of EmSOX2, a member of the Sox family of transcription factors, as a potential regulator of Echinococcus multilocularis germinative cells

Cited by 8 publications

References 37 publications

Genome-wide transcriptome analysis of Echinococcus multilocularis larvae and germinative cell cultures reveals genes involved in parasite stem cell function

Genome-wide transcriptome analysis of Echinococcus multilocularis larvae and germinative cell cultures reveals genes involved in parasite stem cell function

Stem cell proliferation and differentiation during larval metamorphosis of the model tapewormHymenolepis microstoma

Cell repertoire and proliferation of germinative cells of the model cestode Mesocestoides corti

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