A Comparative Transcriptomic Analysis Reveals Conserved Features of Stem Cell Pluripotency in Planarians and Mammals

Labbé, Raymond; Irimia, Manuel; Currie, Ko W.; Lin, Alexander Y.; Zhu, Shu; Brown, David D. R.; Ross, E. J.; Voisin, Véronique; Bader, Gary D.; Blencowe, Benjamin J.; Pearson, Bret J.

doi:10.1002/stem.1144

Cited by 185 publications

(247 citation statements)

References 42 publications

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“…Gene expression levels were determined using the cRPKM metric, i.e., reads per thousand unique-mappable positions of target transcript sequence per million of mapped reads, as described in Labbe et al (2012).…”

Section: Gene Expression Estimationmentioning

confidence: 99%

Widespread intron retention in mammals functionally tunes transcriptomes

et al. 2014

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Alternative splicing (AS) of precursor RNAs is responsible for greatly expanding the regulatory and functional capacity of eukaryotic genomes. Of the different classes of AS, intron retention (IR) is the least well understood. In plants and unicellular eukaryotes, IR is the most common form of AS, whereas in animals, it is thought to represent the least prevalent form. Using high-coverage poly(A)+ RNA-seq data, we observe that IR is surprisingly frequent in mammals, affecting transcripts from as many as three-quarters of multiexonic genes. A highly correlated set of cis features comprising an ''IR code'' reliably discriminates retained from constitutively spliced introns. We show that IR acts widely to reduce the levels of transcripts that are less or not required for the physiology of the cell or tissue type in which they are detected. This ''transcriptome tuning'' function of IR acts through both nonsense-mediated mRNA decay and nuclear sequestration and turnover of IR transcripts. We further show that IR is linked to a cross-talk mechanism involving localized stalling of RNA polymerase II (Pol II) and reduced availability of spliceosomal components. Collectively, the results implicate a global checkpoint-type mechanism whereby reduced recruitment of splicing components coupled to Pol II pausing underlies widespread IR-mediated suppression of inappropriately expressed transcripts.

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Section: Gene Expression Estimationmentioning

confidence: 99%

Widespread intron retention in mammals functionally tunes transcriptomes

et al. 2014

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“…S1, Table S1; for brevity we have omitted the Smed prefix from the gene names). Recent transcriptional profiles generated from sorted cell populations indicate that most bHLH homologs are expressed in the planarian stem cells and their postmitotic progeny (Labbé et al, 2012;Önal et al, 2012;Resch et al, 2012). To investigate cell-and tissue-specific patterns of bHLH gene expression, we performed whole mount in situ hybridization (WISH).…”

Section: Identification Of Bhlh Family Genes In Planariansmentioning

confidence: 99%

“…Following amputation, planarians are capable of restoring lost body parts from a population of adult pluripotent stem cells called neoblasts (Baguñà, 2012;Elliott and Sánchez Alvarado, 2013). Planarian stem cells share conserved pluripotency determinants with mammalian stem cells (Labbé et al, 2012;Önal et al, 2012;Solana et al, 2012) and serve to replace cells lost during normal physiological cell turnover or after amputation. In contrast to most model organisms currently studied, planarians have the remarkable ability to regenerate their CNS after injury.…”

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confidence: 99%

Genome-wide analysis of the bHLH gene family in planarians identifies factors required for adult neurogenesis and neuronal regeneration

et al. 2013

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In contrast to most well-studied model organisms, planarians have a remarkable ability to completely regenerate a functional nervous system from a pluripotent stem cell population. Thus, planarians provide a powerful model to identify genes required for adult neurogenesis in vivo. We analyzed the basic helix-loop-helix (bHLH) family of transcription factors, many of which are crucial for nervous system development and have been implicated in human diseases. However, their potential roles in adult neurogenesis or central nervous system (CNS) function are not well understood. We identified 44 planarian bHLH homologs, determined their patterns of expression in the animal and assessed their functions using RNAi. We found nine bHLHs expressed in stem cells and neurons that are required for CNS regeneration. Our analyses revealed that homologs of coe, hes (hesl-3) and sim label progenitors in intact planarians, and following amputation we observed an enrichment of coe + and sim + progenitors near the wound site. RNAi knockdown of coe, hesl-3 or sim led to defects in CNS regeneration, including failure of the cephalic ganglia to properly pattern and a loss of expression of distinct neuronal subtype markers. Together, these data indicate that coe, hesl-3 and sim label neural progenitor cells, which serve to generate new neurons in uninjured or regenerating animals. Our study demonstrates that this model will be useful to investigate how stem cells interpret and respond to genetic and environmental cues in the CNS and to examine the role of bHLH transcription factors in adult tissue regeneration.

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“…Several groups have developed FACS-based methodologies to isolate different cell populations into the following three categories based on nuclear density and sensitivity to irradiation: X1 cells that primarily consist of proliferating neoblasts (∼90%); X2 cells comprised of a heterogeneous mixture of neoblast progeny (∼70%) and early and late progenitors (∼30%); and Xins cells that mostly consist of terminally differentiated cells (Hayashi et al 2006;Eisenhoffer et al 2008). Comparative transcriptome analyses have identified several genes that are commonly expressed in planarian neoblasts and embryonic stem cells from higher metazoans, suggesting that the pathways that regulate or confer pluripotency may be highly conserved (Labbé et al 2012;Onal et al 2012;Resch et al 2012;Solana et al 2012). Recent studies based on small RNA sequencing from irradiated animals and from neoblast populations identified miRNAs that are specifically enriched in neoblasts (Friedländer et al 2009;Lu et al 2009).…”

Section: Several Mirnas Are Differentially Enriched In Neoblast Subpomentioning

confidence: 99%

Identification of neoblast- and regeneration-specific miRNAs in the planarian Schmidtea mediterranea

Sasidharan

Bansal

et al. 2013

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In recent years, the planarian Schmidtea mediterranea has emerged as a tractable model system to study stem cell biology and regeneration. MicroRNAs are small RNA species that control gene expression by modulating translational repression and mRNA stability and have been implicated in the regulation of various cellular processes. Though recent studies have identified several miRNAs in S. mediterranea, their expression in neoblast subpopulations and during regeneration has not been examined. Here, we identify several miRNAs whose expression is enriched in different neoblast subpopulations and in regenerating tissue at different time points in S. mediterranea. Some of these miRNAs were enriched within 3 h postamputation and may, therefore, play a role in wound healing and/or neoblast migration. Our results also revealed miRNAs, such as sme-miR-2d-3p and the sme-miR-124 family, whose expression is enriched in the cephalic ganglia, are also expressed in the brain primordium during CNS regeneration. These results provide new insight into the potential biological functions of miRNAs in neoblasts and regeneration in planarians.

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A Comparative Transcriptomic Analysis Reveals Conserved Features of Stem Cell Pluripotency in Planarians and Mammals

Cited by 185 publications

References 42 publications

Widespread intron retention in mammals functionally tunes transcriptomes

Widespread intron retention in mammals functionally tunes transcriptomes

Genome-wide analysis of the bHLH gene family in planarians identifies factors required for adult neurogenesis and neuronal regeneration

Identification of neoblast- and regeneration-specific miRNAs in the planarian Schmidtea mediterranea

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