Naturally occurring tumours in the basal metazoan Hydra.
Ontology highlight
ABSTRACT: The molecular nature of malignant tumors is well studied in vertebrates, while their evolutionary origin remains unknown. In particular, there is no evidence for naturally occurring malignant tumors in pre-bilaterian animals, such as sponges and cnidarians. This is somewhat surprising given that recent computational studies have predicted that all metazoans are prone to develop tumors. Here we provide first evidence for naturally occurring tumors in Hydra oligactis. Histological, cellular and molecular data reveal that these tumors are transplantable and caused by differentiation arrest of female gametes. Growth of tumor cells is independent from the cellular environment. Tumor bearing polyps have significantly reduced fitness. In addition, Hydra tumors show a greatly altered transcriptome that mimics expression shifts in vertebrate cancers. Therefore, this study shows, that invasive tumors have deep roots in animal phylogeny, and that early branching animals may be informative in revealing the fundamental mechanisms of tumorigenesis.
Project description:The molecular nature of malignant tumors is well studied in vertebrates, while their evolutionary origin remains unknown. In particular, there is no evidence for naturally occurring malignant tumors in pre-bilaterian animals, such as sponges and cnidarians. This is somewhat surprising given that recent computational studies have predicted that all metazoans are prone to develop tumors. Here we provide first evidence for naturally occurring tumors in Hydra oligactis. Histological, cellular and molecular data reveal that these tumors are transplantable and caused by differentiation arrest of female gametes. Growth of tumor cells is independent from the cellular environment. Tumor bearing polyps have significantly reduced fitness. In addition, Hydra tumors show a greatly altered transcriptome that mimics expression shifts in vertebrate cancers. Therefore, this study shows, that invasive tumors have deep roots in animal phylogeny, and that early branching animals may be informative in revealing the fundamental mechanisms of tumorigenesis. We compared four samples of Hydra oligactis tumor-bearing animals to three samples of female polyps undergoing oogenesis and six samples of female asexual control polyps
Project description:The cnidarian model organism Hydra has long been studied for its remarkable ability to regenerate its head, which is controlled by a head organizer located near the hypostome. Cnidarians and bilaterians diverged about 600 millions years ago but the gene contents of species of both phyla are surprisingly similar despite divergent morphologies and functions. While little is known about the role of cis-regulatory elements in cnidarians, understanding gene regulatory mechanisms in cnidarians can potentially shed light on metazoan evolution. The canonical Wnt pathway plays a central role in head organizer function during regeneration and during bud formation, which is the asexual mode of reproduction in Hydra. However, it is unclear how shared the developmental programs of head organizer genesis are in budding and regeneration. Time-series analysis of gene expression changes during head regeneration and budding revealed a set of 298 differentially expressed genes during the 48-hour head regeneration and 72-hour budding time-courses. In order to understand the regulatory elements controlling hydra head regeneration, we first identified 27,137 open-chromatin elements that are open in one or more sections of organism. We used histone modification ChIP-seq to identify 9998 candidate proximal promoter and 3018 candidate enhancer-like regions respectively. We show that a subset of these regulatory elements is dynamically remodeled during head regeneration and identify a set of transcription factor motifs that are enriched in the enhancer regions activated during head regeneration. Our results show that Hydra displays complex gene regulatory structures of developmentally dynamic enhancers, which suggests that the evolution of complex developmental enhancers predates the split of cnidarians and bilaterians.
Project description:The cnidarian model organism Hydra has long been studied for its remarkable ability to regenerate its head, which is controlled by a head organizer located near the hypostome. Cnidarians and bilaterians diverged about 600 millions years ago but the gene contents of species of both phyla are surprisingly similar despite divergent morphologies and functions. While little is known about the role of cis-regulatory elements in cnidarians, understanding gene regulatory mechanisms in cnidarians can potentially shed light on metazoan evolution. The canonical Wnt pathway plays a central role in head organizer function during regeneration and during bud formation, which is the asexual mode of reproduction in Hydra. However, it is unclear how shared the developmental programs of head organizer genesis are in budding and regeneration. Time-series analysis of gene expression changes during head regeneration and budding revealed a set of 298 differentially expressed genes during the 48-hour head regeneration and 72-hour budding time-courses. In order to understand the regulatory elements controlling hydra head regeneration, we first identified 27,137 open-chromatin elements that are open in one or more sections of organism. We used histone modification ChIP-seq to identify 9998 candidate proximal promoter and 3018 candidate enhancer-like regions respectively. We show that a subset of these regulatory elements is dynamically remodeled during head regeneration and identify a set of transcription factor motifs that are enriched in the enhancer regions activated during head regeneration. Our results show that Hydra displays complex gene regulatory structures of developmentally dynamic enhancers, which suggests that the evolution of complex developmental enhancers predates the split of cnidarians and bilaterians.
Project description:The cnidarian model organism Hydra has long been studied for its remarkable ability to regenerate its head, which is controlled by a head organizer located near the hypostome. Cnidarians and bilaterians diverged about 600 millions years ago but the gene contents of species of both phyla are surprisingly similar despite divergent morphologies and functions. While little is known about the role of cis-regulatory elements in cnidarians, understanding gene regulatory mechanisms in cnidarians can potentially shed light on metazoan evolution. The canonical Wnt pathway plays a central role in head organizer function during regeneration and during bud formation, which is the asexual mode of reproduction in Hydra. However, it is unclear how shared the developmental programs of head organizer genesis are in budding and regeneration. Time-series analysis of gene expression changes during head regeneration and budding revealed a set of 298 differentially expressed genes during the 48-hour head regeneration and 72-hour budding time-courses. In order to understand the regulatory elements controlling hydra head regeneration, we first identified 27,137 open-chromatin elements that are open in one or more sections of organism. We used histone modification ChIP-seq to identify 9998 candidate proximal promoter and 3018 candidate enhancer-like regions respectively. We show that a subset of these regulatory elements is dynamically remodeled during head regeneration and identify a set of transcription factor motifs that are enriched in the enhancer regions activated during head regeneration. Our results show that Hydra displays complex gene regulatory structures of developmentally dynamic enhancers, which suggests that the evolution of complex developmental enhancers predates the split of cnidarians and bilaterians.
Project description:This study aimed to identify the total proteome of Hydra vulgaris, a freshwater polyp, belongs to the cnidarians family with feature of not having a visual eye, while being sensitive to light. Proteins were identified using a combination of gel electrophoresis and data-independent nanoflow liquid chromatography mass spectrometry resulting in the identification of more than 5,200 proteins from all cellular components
Project description:Positional RNA-sequencing of isolated Hydra body pieces and RNA-sequencing of fully regenerated Hydra animal was combined with RNA-sequencing of actively regenerating spheroids (see submission E-MTAB-9672) in order to elucidate the role of tissue stretching on regeneration and body pattern formation.
Project description:Comparative proteome of extracted Hydra vulgaris AEP extracellular matrix form Wnt9/10 knock out and Azakenpaullone treated animals. Used to analyse the changes in molecular composition of the mesoglea (ECM) of normal and Wnt depleted animals