The PIWI proteins SMEDWI-2 and SMEDWI-3 are required for stem cell function and piRNA expression in planarians

Palakodeti, Dasaradhi; Smielewska, Magda; Lu, Yi-Chien; Yeo, G; Graveley, Brenton R.

doi:10.1261/rna.1085008

Cited by 224 publications

(271 citation statements)

References 47 publications

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“…2 E-G, bar graphs). Intergenic piRNAs have very high expression in neoblasts (Ͼ10-fold higher than in untreated whole-body planarians) and low expression in irradiated planarians (4-fold lower than in untreated planarians), consistent with the idea that piRNAs may be up-regulated in neoblasts and their division progeny, i.e., where PIWI proteins are specifically expressed (10). In contrast, total miRNA contents appeared roughly constant over the 3 samples, although the abundances of individual miRNAs varied.…”

Section: Comprehensive and Quantitative Deep Sequencing Of Planarian supporting

confidence: 73%

“…Furthermore, our data contain the lowly expressed ''star'' miRNAs for 62 of the 63 miRNA genes. Another recent study reported Ϸ4,800 planarian piRNAs deep-sequenced from whole-body samples of planarians (10). We found 38% of these piRNAs in our data.…”

Section: Comprehensive and Quantitative Deep Sequencing Of Planarian supporting

confidence: 68%

“…Additionally, all known planarian miRNAs have been identified by classic cloning and Sanger sequencing, and it is highly likely that the true number of planarian miRNAs is much higher. A recent study (10) has further identified a few thousand piRNAs, which is also almost certainly a vast underestimate of the true number of planarian piRNAs (14).…”

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confidence: 96%

“…PIWI proteins are essential for the biogenesis and function of piRNAs, and they appear to have undergone an expansion in the planarian genome. We have identified at least 7 likely planarian PIWI genes, of which 3 (SMEDWI-1-3) have been in part functionally characterized (9,10). For example, depletion of SMEDWI-2 has been shown to generate specific defects in stem-cell-mediated regeneration and homeostasis (9).…”

mentioning

confidence: 99%

“…For example, depletion of SMEDWI-2 has been shown to generate specific defects in stem-cell-mediated regeneration and homeostasis (9). Because neoblasts can give rise to germ-line cells in planaria, it is perhaps not surprising that at least SMEDWI-1 and SMEDWI-2 proteins are specifically expressed in neoblasts, and that depletion of SMEDWI-2 or SMEDWI-3 reduces piRNA production and both are required for neoblast function and regeneration (10).…”

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confidence: 99%

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High-resolution profiling and discovery of planarian small RNAs

Friedländer

Adamidi

Han

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

128

119

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Freshwater planarian flatworms possess uncanny regenerative capacities mediated by abundant and collectively totipotent adult stem cells. Key functions of these cells during regeneration and tissue homeostasis have been shown to depend on PIWI, a molecule required for Piwi-interacting RNA (piRNA) expression in planarians. Nevertheless, the full complement of piRNAs and microRNAs (miRNAs) in this organism has yet to be defined. Here we report on the large-scale cloning and sequencing of small RNAs from the planarian Schmidtea mediterranea, yielding altogether millions of sequenced, unique small RNAs. We show that piRNAs are in part organized in genomic clusters and that they share characteristic features with mammalian and fly piRNAs. We further identify 61 novel miRNA genes and thus double the number of known planarian miRNAs. Sequencing, as well as quantitative PCR of small RNAs, uncovered 10 miRNAs enriched in planarian stem cells. These miRNAs are downregulated in animals in which stem cells have been abrogated by irradiation, and thus constitute miRNAs likely associated with specific stem-cell functions. Altogether, we present the first comprehensive small RNA analysis in animals belonging to the third animal superphylum, the Lophotrochozoa, and single out a number of miRNAs that may function in regeneration. Several of these miRNAs are deeply conserved in animals.microRNAs ͉ miRNAs ͉ piRNAs ͉ regeneration ͉ stem cells P lanarians have become a molecularly tractable model system in which to study regeneration, tissue homeostasis, and stem-cell biology (1). Planaria are free-living, triploblastic flatworms of the phylum Platyhelminthes, which is presently considered to belong to the superphylum Lophotrochozoa. Model systems for modern molecular and developmental biology have almost exclusively focused on the other 2 superphyla, i.e., the Deuterostomes (which includes vertebrates) and the Ecdysozoa (e.g., Caenorhabditis elegans and Drosophila melanogaster). Unlike these model systems, planarians possess remarkable regeneration abilities. Decapitation, for example, results in the complete regeneration of the head within 7 days after amputation. Such robust restoration of missing body parts is mediated by adult stem cells known as neoblasts (2). Of the thousands of known planarian species, Schmidtea mediterranea is arguably the species of choice for modern molecular biology and high-throughput, genome-wide approaches because it is diploid, it exists in sexual and asexual strains, and its genome has recently been sequenced and annotated (3). The size of its genome is roughly a third of the human genome, and Ϸ80% of the Ϸ20,000 annotated planarian genes have orthologs in humans. Moreover, by morphology alone, neoblasts and their immediate division progeny comprise Ϸ25% of all cells in the adult animal (4). In addition, RNAi screens have identified hundreds of genes specifically linked to planarian regeneration and stem-cell biology (5). Many of these genes are conserved in humans, and thus understanding planarian ...

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Section: Comprehensive and Quantitative Deep Sequencing Of Planarian supporting

confidence: 73%

Section: Comprehensive and Quantitative Deep Sequencing Of Planarian supporting

confidence: 68%

mentioning

confidence: 96%

mentioning

confidence: 99%

mentioning

confidence: 99%

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High-resolution profiling and discovery of planarian small RNAs

Friedländer

Adamidi

Han

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

128

119

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An Introduction to Planarians and Their Stem Cells

Aboukhatwa

Aboobaker

2015

Encyclopedia of Life Sciences

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Of all animals, it is perhaps planarians that have the greatest ability to regenerate. These once classical classroom organisms have now become the subject of advanced molecular genetic studies that have the potential to inform us about our own biology. Regeneration relies upon a population of pluripotent adult stem cells, called neoblasts. These collectively pluripotent stem cells underpin the regenerative capacity of planarians. The underlying molecular mechanisms controlling their proliferation, self‐renewal and differentiation are now being described. In particular, progress has been made in describing the expression profile of these cells and identifying some of the molecular mechanisms that regulate their behaviour leading to a better understanding of how these cells power regeneration. Key Concepts Planarians are bilaterians and share many cell and tissue types with other animals including vertebrates. Planarians are able to mount a profound regenerative response to wounding allowing even small fragments to regenerate whole new worms. Planarian regeneration requires the proliferation and differentiation of a population of pluripotent stem cell population called neoblasts. Expression profiling of the neoblast population shows they are a heterogeneous population and express gene regulatory networks in common with both somatic and germline stem cells Many cell biological and molecular genetic approaches can be used to study gene function in planarians allowing novel biological insights to be made, relevant to our own biology. Current research has uncovered many important regulatory processes that regulate stem cells, including those regulated by transcription factors, chromatin modification and RNA binding proteins. Future work will uncover the detailed mechanisms that control stem cell proliferation, self‐renewal and differentiation as well as how missing structures are accurately restored.

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The PIWI‐Interacting RNA Molecular Pathway: Insights From Cultured Silkworm Germline Cells

Sakakibara

Siomi

2017

BioEssays

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The PIWI-interacting RNA (piRNA) pathway, one of the major eukaryotic small RNA silencing pathways, is a genome surveillance system that silences selfish genes in animal gonads. piRNAs guide PIWI protein to target genes through Watson-Crick RNA-RNA base-parings. Loss of piRNA function causes genome instability, inducing failure in gametogenesis and infertility. Studies using fruit flies and mice as key experimental models have resulted in tremendous progress in understanding the mechanism underlying the piRNA pathway. Recent work using cultured silkworm germline cells has also expanded our knowledge of piRNA biogenesis in particular, since these silkworm cells are the only cells of germline origin that can be cultured. In this review, we describe elucidation of the piRNA pathway using cultured silkworm cells as an experimental model by focusing on recent work in biochemistry and structural biology. Earlier studies that made important contributions to the field are also described.

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The PIWI proteins SMEDWI-2 and SMEDWI-3 are required for stem cell function and piRNA expression in planarians

Cited by 224 publications

References 47 publications

High-resolution profiling and discovery of planarian small RNAs

High-resolution profiling and discovery of planarian small RNAs

An Introduction to Planarians and Their Stem Cells

The PIWI‐Interacting RNA Molecular Pathway: Insights From Cultured Silkworm Germline Cells

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