Fibrillarin homologs are required for divergent cell lineage development by translational regulation in planarian homeostasis and regeneration
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ABSTRACT:
ORGANISM(S): Schmidtea mediterranea
PROVIDER: GSE255595 | GEO | 2024/11/13
REPOSITORIES: GEO
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Project description:Translational regulation in adult regenerative tissue remains unclear. Planarians, renowned for remarkable cell turnover and tissue regeneration capabilities, are regenerative flatworms that provide an ideal model to address the gap in knowledge between translational control and cell turnover during adult tissue homeostasis and regeneration. Fibrillarin (FBL) is an RNA 2-O’-methyltransferase crucial for rRNA processing, playing a pivotal role in translational regulation. We explored this in planarian Schmidtea mediterranea and identified two FBL homologs: Smed-fbl-1 (fbl-1) and Smed-fbl-2 (fbl-2) are essential for homeostasis and regeneration, but have distinct roles. fbl-1 is enriched in neoblasts and essential for multiple progenitor cell differentiation. Conversely, fbl-2 is expressed in egr5+ epidermal progenitors, crucial for late-stage epidermal lineage specification. Knockdown (KD) of fbl-1 and fbl-2 resulted in different 2-O’-methylation patterns, suggesting their influence on specific mRNA translation during regeneration. Riboseq analysis revealed that fbl-1 KD reduced the translation of genes associated with alternative splicing, cell cycle, and DNA replication, while fbl-2 KD reduced the translation of genes related to protein stability. Interestingly, fbl-2+ cells spatially correlated with wnt-1+ cells, hinting at fbl-2’s role in its localization. Our study indicated that duplicate fbl genes may have a compensatory role in the development of specific cell lineages. This finding underscores the significance of rRNA modification in translation regulation during the maintenance and regeneration of adult tissues.
2024-11-13 | GSE255594 | GEO
Project description:Translational regulation in adult regenerative tissue remains unclear. Planarians, renowned for remarkable cell turnover and tissue regeneration capabilities, are regenerative flatworms that provide an ideal model to address the gap in knowledge between translational control and cell turnover during adult tissue homeostasis and regeneration. Fibrillarin (FBL) is an RNA 2-O’-methyltransferase crucial for rRNA processing, playing a pivotal role in translational regulation. We explored this in planarian Schmidtea mediterranea and identified two FBL homologs: Smed-fbl-1 (fbl-1) and Smed-fbl-2 (fbl-2) are essential for homeostasis and regeneration, but have distinct roles. fbl-1 is enriched in neoblasts and essential for multiple progenitor cell differentiation. Conversely, fbl-2 is expressed in egr5+ epidermal progenitors, crucial for late-stage epidermal lineage specification. Knockdown (KD) of fbl-1 and fbl-2 resulted in different 2-O’-methylation patterns, suggesting their influence on specific mRNA translation during regeneration. Riboseq analysis revealed that fbl-1 KD reduced the translation of genes associated with alternative splicing, cell cycle, and DNA replication, while fbl-2 KD reduced the translation of genes related to protein stability. Interestingly, fbl-2+ cells spatially correlated with wnt-1+ cells, hinting at fbl-2’s role in its localization. Our study indicated that duplicate fbl genes may have a compensatory role in the development of specific cell lineages. This finding underscores the significance of rRNA modification in translation regulation during the maintenance and regeneration of adult tissues.
2024-11-13 | GSE255590 | GEO
Project description:Abstract: Tissue homeostasis and regeneration involve complex cellular changes. The role of rRNA modification-dependent translational regulation in these processes remains largely unknown. Planarians, renowned for their ability to undergo remarkable tissue regeneration, provide an ideal model for the analysis of differential rRNA regulation in diverse cell types during tissue homeostasis and regeneration. We investigated the role of RNA 2'-O-methyltransferase, Fibrillarin (FBL), in the planarian Schmidtea mediterranea and identified two FBL homologs: Smed-fbl-1 (fbl-1) and Smed-fbl-2 (fbl-2). Both are essential for planarian regeneration, but play distinct roles: fbl-1 is crucial for progenitor cell differentiation, while fbl-2 is important for late-stage epidermal lineage specification. Different 2'-O-methylation patterns were observed upon fbl-1 and fbl-2 knockdown, suggesting their roles in translation of specific mRNA pools during regeneration. Ribo-seq analysis further revealed differing impacts of fbl-1 and fbl-2 knockdown on gene translation. These findings indicate divergent roles of the duplicate fbl genes in specific cell lineage development in planarians and suggest a role of rRNA modifications in translational regulation during tissue maintenance and regeneration.
| S-SCDT-10_1038-S44318-024-00315-X | biostudies-other
Project description:Fibrillarin homologs are required for divergent cell lineage development by translational regulation in planarian homeostasis and regeneration
| PRJNA1075694 | ENA
Project description:Fibrillarin homologs are required for divergent cell lineage development by translational regulation in planarian homeostasis and regeneration [Ribo-seq]
| PRJNA1083472 | ENA
Project description:Fibrillarin homologs are required for divergent cell lineage development by translational regulation in planarian homeostasis and regeneration [RiboMeth-Seq]
| PRJNA1075681 | ENA
Project description:The planarian flatworm is an emerging model that is useful for studying homeostasis and regeneration due to its unique adult stem cells (ASCs). Previously, planaria were found to share mammalian TTAGGG chromosome ends and telomerases; however, their telomere protection proteins have not yet been identified. In Schmidtea mediterranea, we identified a homologue of the human protection of telomeres 1 (POT1) with an OB-fold (SmedOB1). SmedOB1 is evolutionarily conserved among species and is ubiquitously expressed throughout the whole body. Feeding with SmedOB1 double-stranded RNAs (dsRNAs) led to homeostasis abnormalities in the head and pharynx. Furthermore, several ASC progeny markers were downregulated, and regeneration was impaired. Here we found that SmedOB1 is required for telomeric DNA-protein complex formation and it associates with the telomere TTAGGG sequence in vitro. Moreover, DNA damage and apoptosis signals in planarian were significantly affected by SmedOB1 RNAi. We also confirmed these phenotypes in Dugesia japonica, another flatworm species. Our work identified a novel telomere-associated protein SmedOB1 in planarian, which is required for planarian homeostasis and regeneration. The phylogenetic and functional conservations of SmedOB1 provide one mechanism by which planarians maintain telomere and genome stability to ensure their immortality and shed light on the regeneration medicine of humans.
| S-EPMC5032016 | biostudies-literature
Project description:We have identified two genes, Smed-PTEN-1 and Smed-PTEN-2, capable of regulating stem cell function in the planarian Schmidtea mediterranea. Both genes encode proteins homologous to the mammalian tumor suppressor, phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Inactivation of Smed-PTEN-1 and -2 by RNA interference (RNAi) in planarians disrupts regeneration, and leads to abnormal outgrowths in both cut and uncut animals followed soon after by death (lysis). The resulting phenotype is characterized by hyperproliferation of neoblasts (planarian stem cells), tissue disorganization and a significant accumulation of postmitotic cells with impaired differentiation capacity. Further analyses revealed that rapamycin selectively prevented such accumulation without affecting the normal neoblast proliferation associated with physiological turnover and regeneration. In animals in which PTEN function is abrogated, we also detected a significant increase in the number of cells expressing the planarian Akt gene homolog (Smed-Akt). However, functional abrogation of Smed-Akt in Smed-PTEN RNAi-treated animals does not prevent cell overproliferation and lethality, indicating that functional abrogation of Smed-PTEN is sufficient to induce abnormal outgrowths. Altogether, our data reveal roles for PTEN in the regulation of planarian stem cells that are strikingly conserved to mammalian models. In addition, our results implicate this protein in the control of stem cell maintenance during the regeneration of complex structures in planarians.
| S-EPMC2562200 | biostudies-literature
Project description:After amputation, freshwater planarians properly regenerate a head or tail from the resulting anterior or posterior wound. The mechanisms that differentiate anterior from posterior and direct the replacement of the appropriate missing body parts are unknown. We found that in the planarian Schmidtea mediterranea, RNA interference (RNAi) of beta-catenin or dishevelled causes the inappropriate regeneration of a head instead of a tail at posterior amputations. Conversely, RNAi of the beta-catenin antagonist adenomatous polyposis coli results in the regeneration of a tail at anterior wounds. In addition, the silencing of beta-catenin is sufficient to transform the tail of uncut adult animals into a head. We suggest that beta-catenin functions as a molecular switch to specify and maintain anteroposterior identity during regeneration and homeostasis in planarians.
| S-EPMC2755502 | biostudies-literature
Project description:Planarians are an excellent model for investigating molecular mechanisms necessary for regenerating a functional nervous system. Numerous studies have led to the generation of extensive genomic resources, especially whole-animal single-cell RNA-seq resources. These have facilitated in silico predictions of neuronal subtypes, many of which have been anatomically mapped by in situ hybridization. However, our knowledge of the function of dozens of neuronal subtypes remains poorly understood. Previous investigations identified that polycystic kidney disease (pkd)-like genes in planarians are strongly expressed in sensory neurons and have roles in mechanosensation. Here, we examine the expression and function of all the pkd genes found in the Schmidtea mediterranea genome and map their expression in the asexual and hermaphroditic strains. Using custom behavioral assays, we test the function of pkd genes in response to mechanical stimulation and in food detection. Our work provides insight into the physiological function of sensory neuron populations and protocols for creating inexpensive automated setups for acquiring and analyzing mechanosensory stimulation in planarians.
| S-EPMC11291080 | biostudies-literature