Transcriptomic analysis supports a role for the nervous system in regulating growth and development of Fasciola hepatica juveniles.
Fasciola spp. liver flukes have significant impacts in veterinary and human medicine. The absence of a vaccine and increasing anthelmintic resistance threaten sustainable control and underscore the need for novel flukicides. Functional genomic approaches underpinned by in vitro culture of juvenile F...
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ftdoajarticles:oai:doaj.org/article:942dd2f73db1407ab6c0e8a48ec46440 2023-05-15T15:16:12+02:00 Transcriptomic analysis supports a role for the nervous system in regulating growth and development of Fasciola hepatica juveniles. Emily Robb Erin M McCammick Duncan Wells Paul McVeigh Erica Gardiner Rebecca Armstrong Paul McCusker Angela Mousley Nathan Clarke Nikki J Marks Aaron G Maule 2022-11-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0010854 https://doaj.org/article/942dd2f73db1407ab6c0e8a48ec46440 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0010854 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0010854 https://doaj.org/article/942dd2f73db1407ab6c0e8a48ec46440 PLoS Neglected Tropical Diseases, Vol 16, Iss 11, p e0010854 (2022) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2022 ftdoajarticles https://doi.org/10.1371/journal.pntd.0010854 2022-12-30T19:37:37Z Fasciola spp. liver flukes have significant impacts in veterinary and human medicine. The absence of a vaccine and increasing anthelmintic resistance threaten sustainable control and underscore the need for novel flukicides. Functional genomic approaches underpinned by in vitro culture of juvenile Fasciola hepatica facilitate control target validation in the most pathogenic life stage. Comparative transcriptomics of in vitro and in vivo maintained 21 day old F. hepatica finds that 86% of genes are expressed at similar levels across maintenance treatments suggesting commonality in core biological functioning within these juveniles. Phenotypic comparisons revealed higher cell proliferation and growth rates in the in vivo juveniles compared to their in vitro counterparts. These phenotypic differences were consistent with the upregulation of neoblast-like stem cell and cell-cycle associated genes in in vivo maintained worms. The more rapid growth/development of in vivo juveniles was further evidenced by a switch in cathepsin protease expression profiles, dominated by cathepsin B in in vitro juveniles and by cathepsin L in in vivo juveniles. Coincident with more rapid growth/development was the marked downregulation of both classical and peptidergic neuronal signalling components in in vivo maintained juveniles, supporting a role for the nervous system in regulating liver fluke growth and development. Differences in the miRNA complements of in vivo and in vitro juveniles identified 31 differentially expressed miRNAs, including fhe-let-7a-5p, fhe-mir-124-3p and miRNAs predicted to target Wnt-signalling, which supports a key role for miRNAs in driving the growth/developmental differences in the in vitro and in vivo maintained juvenile liver fluke. Widespread differences in the expression of neuronal genes in juvenile fluke grown in vitro and in vivo expose significant interplay between neuronal signalling and the rate of growth/development, encouraging consideration of neuronal targets in efforts to dysregulate ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 16 11 e0010854 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Emily Robb Erin M McCammick Duncan Wells Paul McVeigh Erica Gardiner Rebecca Armstrong Paul McCusker Angela Mousley Nathan Clarke Nikki J Marks Aaron G Maule Transcriptomic analysis supports a role for the nervous system in regulating growth and development of Fasciola hepatica juveniles. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Fasciola spp. liver flukes have significant impacts in veterinary and human medicine. The absence of a vaccine and increasing anthelmintic resistance threaten sustainable control and underscore the need for novel flukicides. Functional genomic approaches underpinned by in vitro culture of juvenile Fasciola hepatica facilitate control target validation in the most pathogenic life stage. Comparative transcriptomics of in vitro and in vivo maintained 21 day old F. hepatica finds that 86% of genes are expressed at similar levels across maintenance treatments suggesting commonality in core biological functioning within these juveniles. Phenotypic comparisons revealed higher cell proliferation and growth rates in the in vivo juveniles compared to their in vitro counterparts. These phenotypic differences were consistent with the upregulation of neoblast-like stem cell and cell-cycle associated genes in in vivo maintained worms. The more rapid growth/development of in vivo juveniles was further evidenced by a switch in cathepsin protease expression profiles, dominated by cathepsin B in in vitro juveniles and by cathepsin L in in vivo juveniles. Coincident with more rapid growth/development was the marked downregulation of both classical and peptidergic neuronal signalling components in in vivo maintained juveniles, supporting a role for the nervous system in regulating liver fluke growth and development. Differences in the miRNA complements of in vivo and in vitro juveniles identified 31 differentially expressed miRNAs, including fhe-let-7a-5p, fhe-mir-124-3p and miRNAs predicted to target Wnt-signalling, which supports a key role for miRNAs in driving the growth/developmental differences in the in vitro and in vivo maintained juvenile liver fluke. Widespread differences in the expression of neuronal genes in juvenile fluke grown in vitro and in vivo expose significant interplay between neuronal signalling and the rate of growth/development, encouraging consideration of neuronal targets in efforts to dysregulate ... |
format |
Article in Journal/Newspaper |
author |
Emily Robb Erin M McCammick Duncan Wells Paul McVeigh Erica Gardiner Rebecca Armstrong Paul McCusker Angela Mousley Nathan Clarke Nikki J Marks Aaron G Maule |
author_facet |
Emily Robb Erin M McCammick Duncan Wells Paul McVeigh Erica Gardiner Rebecca Armstrong Paul McCusker Angela Mousley Nathan Clarke Nikki J Marks Aaron G Maule |
author_sort |
Emily Robb |
title |
Transcriptomic analysis supports a role for the nervous system in regulating growth and development of Fasciola hepatica juveniles. |
title_short |
Transcriptomic analysis supports a role for the nervous system in regulating growth and development of Fasciola hepatica juveniles. |
title_full |
Transcriptomic analysis supports a role for the nervous system in regulating growth and development of Fasciola hepatica juveniles. |
title_fullStr |
Transcriptomic analysis supports a role for the nervous system in regulating growth and development of Fasciola hepatica juveniles. |
title_full_unstemmed |
Transcriptomic analysis supports a role for the nervous system in regulating growth and development of Fasciola hepatica juveniles. |
title_sort |
transcriptomic analysis supports a role for the nervous system in regulating growth and development of fasciola hepatica juveniles. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2022 |
url |
https://doi.org/10.1371/journal.pntd.0010854 https://doaj.org/article/942dd2f73db1407ab6c0e8a48ec46440 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 16, Iss 11, p e0010854 (2022) |
op_relation |
https://doi.org/10.1371/journal.pntd.0010854 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0010854 https://doaj.org/article/942dd2f73db1407ab6c0e8a48ec46440 |
op_doi |
https://doi.org/10.1371/journal.pntd.0010854 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
16 |
container_issue |
11 |
container_start_page |
e0010854 |
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1766346491859828736 |