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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-11-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | https://doi.org/10.1371/journal.pntd.0010854 |
| _version_ | 1811179559726350336 |
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| 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 |
| collection | DOAJ |
| 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 growth/development for parasite control. |
| first_indexed | 2024-04-11T06:36:22Z |
| format | Article |
| id | doaj.art-942dd2f73db1407ab6c0e8a48ec46440 |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-04-11T06:36:22Z |
| publishDate | 2022-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-942dd2f73db1407ab6c0e8a48ec464402022-12-22T04:39:41ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352022-11-011611e001085410.1371/journal.pntd.0010854Transcriptomic analysis supports a role for the nervous system in regulating growth and development of Fasciola hepatica juveniles.Emily RobbErin M McCammickDuncan WellsPaul McVeighErica GardinerRebecca ArmstrongPaul McCuskerAngela MousleyNathan ClarkeNikki J MarksAaron G MauleFasciola 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 growth/development for parasite control.https://doi.org/10.1371/journal.pntd.0010854 |
| spellingShingle | 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. PLoS Neglected Tropical Diseases |
| title | 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_short | 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 |
| url | https://doi.org/10.1371/journal.pntd.0010854 |
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