The Experts below are selected from a list of 303 Experts worldwide ranked by ideXlab platform
Phillip A Newmark - One of the best experts on this subject based on the ideXlab platform.
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the esophageal gland mediates host immune evasion by the Human Parasite schistosoma mansoni
Proceedings of the National Academy of Sciences of the United States of America, 2020Co-Authors: Jayhun Lee, Tracy Chong, Phillip A NewmarkAbstract:Schistosomes are parasitic flatworms that cause schistosomiasis, a neglected tropical disease affecting over 200 million people. Schistosomes develop multiple body plans while navigating their complex life cycle, which involves two different hosts: a mammalian definitive host and a molluscan intermediate host. Their survival and propagation depend upon proliferation and differentiation of stem cells necessary for Parasite homeostasis and reproduction. Infective larvae released from snails carry a handful of stem cells that serve as the likely source of new tissues as the Parasite adapts to life inside the mammalian host; however, the role of these stem cells during this critical life cycle stage remains unclear. Here, we characterize stem cell fates during early intramammalian development. Surprisingly, we find that the esophageal gland, an accessory organ of the digestive tract, develops before the rest of the digestive system is formed and blood feeding is initiated, suggesting a role in processes beyond nutrient uptake. To explore such a role, we examine schistosomes that lack the esophageal gland due to knockdown of a forkhead-box transcription factor, Sm-foxA, which blocks development and maintenance of the esophageal gland, without affecting the development of other somatic tissues. Intriguingly, schistosomes lacking the esophageal gland die after transplantation into naive mice, but survive in immunodeficient mice lacking B cells. We show that Parasites lacking the esophageal gland are unable to lyse ingested immune cells within the esophagus before passing them into the gut. These results unveil an immune-evasion mechanism mediated by the esophageal gland, which is essential for schistosome survival and pathogenesis.
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adult somatic stem cells in the Human Parasite schistosoma mansoni
Nature, 2013Co-Authors: James J Collins, Bo Wang, Bramwell G Lambrus, Marla E Tharp, Harini Iyer, Phillip A NewmarkAbstract:This study reports the identification of adult stem cells in the Human Parasite Schistosoma mansoni (blood fluke); the cells proliferate and differentiate into derivatives of multiple germ layers, and their maintenance requires a fibroblast growth factor receptor orthologue. Adult stem cells (or neoblasts) are found in free-living planarians and parasitic tapeworms and can support impressive feats of tissue regeneration. Phillip Newmark and colleagues now report the identification of adult stem cells in the Human Parasite Schistosoma mansoni. This trematode flatworm, also known as the blood fluke, infects millions of people worldwide. The schistosomal stem cells proliferate and differentiate into derivatives of multiple germ layers, and express a fibroblast growth factor receptor orthologue. Using RNA interference, the authors showed that this gene is required for the maintenance of the neoblast-like cells. These findings might help to elucidate the mechanisms that promote the Parasite's longevity and so could be relevant for medical treatment. Schistosomiasis is among the most prevalent Human parasitic diseases, affecting more than 200 million people worldwide1. The aetiological agents of this disease are trematode flatworms (Schistosoma) that live and lay eggs within the vasculature of the host. These eggs lodge in host tissues, causing inflammatory responses that are the primary cause of morbidity. Because these Parasites can live and reproduce within Human hosts for decades2, elucidating the mechanisms that promote their longevity is of fundamental importance. Although adult pluripotent stem cells, called neoblasts, drive long-term homeostatic tissue maintenance in long-lived free-living flatworms3,4 (for example, planarians), and neoblast-like cells have been described in some parasitic tapeworms5, little is known about whether similar cell types exist in any trematode species. Here we describe a population of neoblast-like cells in the trematode Schistosoma mansoni. These cells resemble planarian neoblasts morphologically and share their ability to proliferate and differentiate into derivatives of multiple germ layers. Capitalizing on available genomic resources6,7 and RNA-seq-based gene expression profiling, we find that these schistosome neoblast-like cells express a fibroblast growth factor receptor orthologue. Using RNA interference we demonstrate that this gene is required for the maintenance of these neoblast-like cells. Our observations indicate that adaptation of developmental strategies shared by free-living ancestors to modern-day schistosomes probably contributed to the success of these animals as long-lived obligate Parasites. We expect that future studies deciphering the function of these neoblast-like cells will have important implications for understanding the biology of these devastating Parasites.
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adult somatic stem cells in the Human Parasite schistosoma mansoni
Nature, 2013Co-Authors: James J Collins, Bo Wang, Bramwell G Lambrus, Marla E Tharp, Harini Iyer, Phillip A NewmarkAbstract:Schistosomiasis is among the most prevalent Human parasitic diseases, affecting more than 200 million people worldwide. The aetiological agents of this disease are trematode flatworms (Schistosoma) that live and lay eggs within the vasculature of the host. These eggs lodge in host tissues, causing inflammatory responses that are the primary cause of morbidity. Because these Parasites can live and reproduce within Human hosts for decades, elucidating the mechanisms that promote their longevity is of fundamental importance. Although adult pluripotent stem cells, called neoblasts, drive long-term homeostatic tissue maintenance in long-lived free-living flatworms (for example, planarians), and neoblast-like cells have been described in some parasitic tapeworms, little is known about whether similar cell types exist in any trematode species. Here we describe a population of neoblast-like cells in the trematode Schistosoma mansoni. These cells resemble planarian neoblasts morphologically and share their ability to proliferate and differentiate into derivatives of multiple germ layers. Capitalizing on available genomic resources and RNA-seq-based gene expression profiling, we find that these schistosome neoblast-like cells express a fibroblast growth factor receptor orthologue. Using RNA interference we demonstrate that this gene is required for the maintenance of these neoblast-like cells. Our observations indicate that adaptation of developmental strategies shared by free-living ancestors to modern-day schistosomes probably contributed to the success of these animals as long-lived obligate Parasites. We expect that future studies deciphering the function of these neoblast-like cells will have important implications for understanding the biology of these devastating Parasites.
James J Collins - One of the best experts on this subject based on the ideXlab platform.
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Methods for Studying the Germline of the Human Parasite Schistosoma mansoni.
Methods in molecular biology (Clifton N.J.), 2016Co-Authors: Julie N. R. Collins, James J CollinsAbstract:Schistosomes are flatworm Parasites that claim the lives of more than 200,000 people in poverty-stricken regions every year. Much of the pathology due to infection is the direct result of injury spurred by the Parasite's eggs becoming lodged in host tissues. Thus, asking basic questions about germ cell biology may not only identify novel therapeutic approaches, but could also uncover conserved mechanisms that regulate the germline in diverse metazoa. Here, we detail useful methods for studying the schistosome germline including EdU labeling, whole-mount in situ hybridization, and RNA interference. These methods will hopefully lead to new insights about germline development in the schistosome and facilitate new investigators to begin asking questions about these important and fascinating Parasites.
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adult somatic stem cells in the Human Parasite schistosoma mansoni
Nature, 2013Co-Authors: James J Collins, Bo Wang, Bramwell G Lambrus, Marla E Tharp, Harini Iyer, Phillip A NewmarkAbstract:This study reports the identification of adult stem cells in the Human Parasite Schistosoma mansoni (blood fluke); the cells proliferate and differentiate into derivatives of multiple germ layers, and their maintenance requires a fibroblast growth factor receptor orthologue. Adult stem cells (or neoblasts) are found in free-living planarians and parasitic tapeworms and can support impressive feats of tissue regeneration. Phillip Newmark and colleagues now report the identification of adult stem cells in the Human Parasite Schistosoma mansoni. This trematode flatworm, also known as the blood fluke, infects millions of people worldwide. The schistosomal stem cells proliferate and differentiate into derivatives of multiple germ layers, and express a fibroblast growth factor receptor orthologue. Using RNA interference, the authors showed that this gene is required for the maintenance of the neoblast-like cells. These findings might help to elucidate the mechanisms that promote the Parasite's longevity and so could be relevant for medical treatment. Schistosomiasis is among the most prevalent Human parasitic diseases, affecting more than 200 million people worldwide1. The aetiological agents of this disease are trematode flatworms (Schistosoma) that live and lay eggs within the vasculature of the host. These eggs lodge in host tissues, causing inflammatory responses that are the primary cause of morbidity. Because these Parasites can live and reproduce within Human hosts for decades2, elucidating the mechanisms that promote their longevity is of fundamental importance. Although adult pluripotent stem cells, called neoblasts, drive long-term homeostatic tissue maintenance in long-lived free-living flatworms3,4 (for example, planarians), and neoblast-like cells have been described in some parasitic tapeworms5, little is known about whether similar cell types exist in any trematode species. Here we describe a population of neoblast-like cells in the trematode Schistosoma mansoni. These cells resemble planarian neoblasts morphologically and share their ability to proliferate and differentiate into derivatives of multiple germ layers. Capitalizing on available genomic resources6,7 and RNA-seq-based gene expression profiling, we find that these schistosome neoblast-like cells express a fibroblast growth factor receptor orthologue. Using RNA interference we demonstrate that this gene is required for the maintenance of these neoblast-like cells. Our observations indicate that adaptation of developmental strategies shared by free-living ancestors to modern-day schistosomes probably contributed to the success of these animals as long-lived obligate Parasites. We expect that future studies deciphering the function of these neoblast-like cells will have important implications for understanding the biology of these devastating Parasites.
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adult somatic stem cells in the Human Parasite schistosoma mansoni
Nature, 2013Co-Authors: James J Collins, Bo Wang, Bramwell G Lambrus, Marla E Tharp, Harini Iyer, Phillip A NewmarkAbstract:Schistosomiasis is among the most prevalent Human parasitic diseases, affecting more than 200 million people worldwide. The aetiological agents of this disease are trematode flatworms (Schistosoma) that live and lay eggs within the vasculature of the host. These eggs lodge in host tissues, causing inflammatory responses that are the primary cause of morbidity. Because these Parasites can live and reproduce within Human hosts for decades, elucidating the mechanisms that promote their longevity is of fundamental importance. Although adult pluripotent stem cells, called neoblasts, drive long-term homeostatic tissue maintenance in long-lived free-living flatworms (for example, planarians), and neoblast-like cells have been described in some parasitic tapeworms, little is known about whether similar cell types exist in any trematode species. Here we describe a population of neoblast-like cells in the trematode Schistosoma mansoni. These cells resemble planarian neoblasts morphologically and share their ability to proliferate and differentiate into derivatives of multiple germ layers. Capitalizing on available genomic resources and RNA-seq-based gene expression profiling, we find that these schistosome neoblast-like cells express a fibroblast growth factor receptor orthologue. Using RNA interference we demonstrate that this gene is required for the maintenance of these neoblast-like cells. Our observations indicate that adaptation of developmental strategies shared by free-living ancestors to modern-day schistosomes probably contributed to the success of these animals as long-lived obligate Parasites. We expect that future studies deciphering the function of these neoblast-like cells will have important implications for understanding the biology of these devastating Parasites.
Klaus Brehm - One of the best experts on this subject based on the ideXlab platform.
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the unique stem cell system of the immortal larva of the Human Parasite echinococcus multilocularis
Evodevo, 2014Co-Authors: Uriel Koziol, Theresa Rauschendorfer, Luis Zanon Rodriguez, Georg Krohne, Klaus BrehmAbstract:Background It is believed that in tapeworms a separate population of undifferentiated cells, the germinative cells, is the only source of cell proliferation throughout the life cycle (similar to the neoblasts of free living flatworms). In Echinococcus multilocularis, the metacestode larval stage has a unique development, growing continuously like a mass of vesicles that infiltrate the tissues of the intermediate host, generating multiple protoscoleces by asexual budding. This unique proliferation potential indicates the existence of stem cells that are totipotent and have the ability for extensive self-renewal.
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The unique stem cell system of the immortal larva of the Human Parasite Echinococcus multilocularis
EvoDevo, 2014Co-Authors: Uriel Koziol, Theresa Rauschendorfer, Georg Krohne, Luis Zanon Rodríguez, Klaus BrehmAbstract:Background It is believed that in tapeworms a separate population of undifferentiated cells, the germinative cells, is the only source of cell proliferation throughout the life cycle (similar to the neoblasts of free living flatworms). In Echinococcus multilocularis , the metacestode larval stage has a unique development, growing continuously like a mass of vesicles that infiltrate the tissues of the intermediate host, generating multiple protoscoleces by asexual budding. This unique proliferation potential indicates the existence of stem cells that are totipotent and have the ability for extensive self-renewal. Results We show that only the germinative cells proliferate in the larval vesicles and in primary cell cultures that undergo complete vesicle regeneration, by using a combination of morphological criteria and by developing molecular markers of differentiated cell types. The germinative cells are homogeneous in morphology but heterogeneous at the molecular level, since only sub-populations express homologs of the post-transcriptional regulators nanos and argonaute . Important differences are observed between the expression patterns of selected neoblast marker genes of other flatworms and the E. multilocularis germinative cells, including widespread expression in E. multilocularis of some genes that are neoblast-specific in planarians. Hydroxyurea treatment results in the depletion of germinative cells in larval vesicles, and after recovery following hydroxyurea treatment, surviving proliferating cells grow as patches that suggest extensive self-renewal potential for individual germinative cells. Conclusions In E. multilocularis metacestodes, the germinative cells are the only proliferating cells, presumably driving the continuous growth of the larval vesicles. However, the existence of sub-populations of the germinative cells is strongly supported by our data. Although the germinative cells are very similar to the neoblasts of other flatworms in function and in undifferentiated morphology, their unique gene expression pattern and the evolutionary loss of conserved stem cells regulators suggest that important differences in their physiology exist, which could be related to the unique biology of E. multilocularis larvae.
Uriel Koziol - One of the best experts on this subject based on the ideXlab platform.
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the unique stem cell system of the immortal larva of the Human Parasite echinococcus multilocularis
Evodevo, 2014Co-Authors: Uriel Koziol, Theresa Rauschendorfer, Luis Zanon Rodriguez, Georg Krohne, Klaus BrehmAbstract:Background It is believed that in tapeworms a separate population of undifferentiated cells, the germinative cells, is the only source of cell proliferation throughout the life cycle (similar to the neoblasts of free living flatworms). In Echinococcus multilocularis, the metacestode larval stage has a unique development, growing continuously like a mass of vesicles that infiltrate the tissues of the intermediate host, generating multiple protoscoleces by asexual budding. This unique proliferation potential indicates the existence of stem cells that are totipotent and have the ability for extensive self-renewal.
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The unique stem cell system of the immortal larva of the Human Parasite Echinococcus multilocularis
EvoDevo, 2014Co-Authors: Uriel Koziol, Theresa Rauschendorfer, Georg Krohne, Luis Zanon Rodríguez, Klaus BrehmAbstract:Background It is believed that in tapeworms a separate population of undifferentiated cells, the germinative cells, is the only source of cell proliferation throughout the life cycle (similar to the neoblasts of free living flatworms). In Echinococcus multilocularis , the metacestode larval stage has a unique development, growing continuously like a mass of vesicles that infiltrate the tissues of the intermediate host, generating multiple protoscoleces by asexual budding. This unique proliferation potential indicates the existence of stem cells that are totipotent and have the ability for extensive self-renewal. Results We show that only the germinative cells proliferate in the larval vesicles and in primary cell cultures that undergo complete vesicle regeneration, by using a combination of morphological criteria and by developing molecular markers of differentiated cell types. The germinative cells are homogeneous in morphology but heterogeneous at the molecular level, since only sub-populations express homologs of the post-transcriptional regulators nanos and argonaute . Important differences are observed between the expression patterns of selected neoblast marker genes of other flatworms and the E. multilocularis germinative cells, including widespread expression in E. multilocularis of some genes that are neoblast-specific in planarians. Hydroxyurea treatment results in the depletion of germinative cells in larval vesicles, and after recovery following hydroxyurea treatment, surviving proliferating cells grow as patches that suggest extensive self-renewal potential for individual germinative cells. Conclusions In E. multilocularis metacestodes, the germinative cells are the only proliferating cells, presumably driving the continuous growth of the larval vesicles. However, the existence of sub-populations of the germinative cells is strongly supported by our data. Although the germinative cells are very similar to the neoblasts of other flatworms in function and in undifferentiated morphology, their unique gene expression pattern and the evolutionary loss of conserved stem cells regulators suggest that important differences in their physiology exist, which could be related to the unique biology of E. multilocularis larvae.
Thomas Crellen - One of the best experts on this subject based on the ideXlab platform.
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whole genome resequencing of the Human Parasite schistosoma mansoni reveals population history and effects of selection
Scientific Reports, 2016Co-Authors: Nancy Holroyd, Thomas Crellen, Fiona Allan, Sophia David, Caroline Durrant, Thomas Huckvale, Aidan M Emery, David RollinsonAbstract:Schistosoma mansoni is a parasitic fluke that infects millions of people in the developing world. This study presents the first application of population genomics to S. mansoni based on high-coverage resequencing data from 10 global isolates and an isolate of the closely-related Schistosoma rodhaini, which infects rodents. Using population genetic tests, we document genes under directional and balancing selection in S. mansoni that may facilitate adaptation to the Human host. Coalescence modeling reveals the speciation of S. mansoni and S. rodhaini as 107.5–147.6KYA, a period which overlaps with the earliest archaeological evidence for fishing in Africa. Our results indicate that S. mansoni originated in East Africa and experienced a decline in effective population size 20–90KYA, before dispersing across the continent during the Holocene. In addition, we find strong evidence that S. mansoni migrated to the New World with the 16–19th Century Atlantic Slave Trade.