Deep learning of cross-species single-cell landscapes identifies conserved regulatory programs underlying cell types

Nature Genetics, Год журнала: 2022, Номер 54(11), С. 1711 - 1720

Опубликована: Окт. 13, 2022

Язык: Английский

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Ets-1 transcription factor regulates glial cell regeneration and function in planarians

Development, Год журнала: 2023, Номер 150(18)

Опубликована: Сен. 4, 2023

Glia play multifaceted roles in nervous systems response to injury. Depending on the species, extent of injury and glial cell type question, glia can help or hinder regeneration neurons. Studying context successful could reveal features pro-regenerative that be exploited for new human therapies. Planarian flatworms completely regenerate their after - including thus provide a strong model system exploring regeneration. Here, we report planarian neurons, neurons are required correct numbers localization during We also identify transcription factor-encoding gene ets-1 as key regulator maintenance Using (RNAi) perturb glia, show loss is associated with altered neuronal expression, impeded animal movement impaired architecture particularly within neuropil. Importantly, our work reveals inter-relationships robust neural

Язык: Английский

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A comparative analysis of planarian genomes reveals regulatory conservation in the face of rapid structural divergence

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Сен. 18, 2024

Язык: Английский

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Whole-genome analyses converge to support the Hemirotifera hypothesis within Syndermata (Gnathifera)

Hydrobiologia, Год журнала: 2024, Номер 851(12-13), С. 2795 - 2826

Опубликована: Янв. 18, 2024

Язык: Английский

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Genome-wide transcriptome analysis of Echinococcus multilocularis larvae and germinative cell cultures reveals genes involved in parasite stem cell function

Frontiers in Cellular and Infection Microbiology, Год журнала: 2024, Номер 14

Опубликована: Янв. 25, 2024

The lethal zoonosis alveolar echinococcosis is caused by tumour-like growth of the metacestode stage tapeworm Echinococcus multilocularis within host organs. We previously demonstrated that proliferation exclusively driven somatic stem cells (germinative cells), which are only mitotically active parasite give rise to all differentiated cell types. gene repertoire required for germinative maintenance and differentiation has not been characterised so far. herein carried out Illumina sequencing on cDNA from vesicles, tissue depleted cells, primary cultures. identified a set ~1,180 genes associated with contained numerous known markers alongside involved in replication, cycle regulation, mitosis, meiosis, epigenetic modification, nucleotide metabolism. Interestingly, we also 44 transcription factors likely regulating and/or pluripotency. By situ hybridization pulse-chase experiments, found new general marker, EmCIP2Ah, provide evidence implying presence slow cycling sub-population expressing extracellular matrix factor Emkal1. RNA-Seq analyses cultures revealed metacestode-derived display an expanded capability do form types metacestode, but specific protoscoleces, adult worms, oncospheres, including ortholog schistosome praziquantel target, EmTRPMPZQ. Finally, show contain population tumour necrosis α receptor family mammalian TNFα accelerates development vesicles cells. Taken together, our robust comprehensive characterization transcriptome, demonstrate derived underscore potential investigate developmental processes parasite. These data relevant studies into role will facilitate design anti-parasitic drugs specifically act compartment.

Язык: Английский

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m6A is required for resolving progenitor identity during planarian stem cell differentiation

The EMBO Journal, Год журнала: 2022, Номер 41(21)

Опубликована: Авг. 16, 2022

Язык: Английский

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Spatiotemporal transcriptomic atlas reveals the dynamic characteristics and key regulators of planarian regeneration

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Июнь 2, 2023

Abstract Whole-body regeneration of planarians is a natural wonder but how it occurs remains elusive. It requires coordinated responses from each cell in the remaining tissue with spatial awareness to regenerate new cells and missing body parts. While previous studies identified genes essential regeneration, more efficient screening approach that can identify regeneration-associated context needed. Here, we present comprehensive three-dimensional spatiotemporal transcriptomic landscape planarian regeneration. We describe pluripotent neoblast subtype, show depletion its marker gene makes susceptible sub-lethal radiation. Furthermore, expression modules for development. Functional analysis hub modules, such as plk1 , shows their important roles Our atlas provides powerful tool deciphering identifying homeostasis-related genes, publicly available online resource research.

Язык: Английский

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Distinguishing classes of neuroactive drugs based on computational physicochemical properties and experimental phenotypic profiling in planarians

PLoS ONE, Год журнала: 2025, Номер 20(1), С. e0315394 - e0315394

Опубликована: Янв. 30, 2025

Mental illnesses put a tremendous burden on afflicted individuals and society. Identification of novel drugs to treat such conditions is intrinsically challenging due the complexity neuropsychiatric diseases need for systems-level understanding that goes beyond single molecule-target interactions. Thus far, drug discovery approaches focused target-based in silico or vitro high-throughput screening (HTS) have had limited success because they cannot capture pathway interactions predict how compound will affect whole organism. Organismal behavioral testing needed fill gap, but mammalian studies are too time-consuming cost-prohibitive early stages discovery. Behavioral medium-throughput (MTS) small organisms promises address this complement HTS improve neuroactive compounds. Here, we used cheminformatics MTS freshwater planarian Dugesia japonica –an invertebrate system neurotoxicant testing–to evaluate extent which complementary insight could be gained from two data streams. In pilot study, our goal was classify 19 compounds into their functional categories: antipsychotics, anxiolytics, antidepressants. Drug classification performed with same computational methods, using either physicochemical descriptors profiling. As it not obvious priori method most suited task, compared performance four approaches. We principal coordinate analysis uniform manifold approximation projection, each coupled linear discriminant analysis, types machine learning models–artificial neural net ensembles support vector machines. Classification based properties comparable accuracy profiling, especially models all accuracies 90–100%. Planarian correctly identified multiple therapeutic uses, thus yielding additional information cheminformatics. Given an inexpensive true 3R (refine, reduce, replace) alternative vertebrate requires zero knowledge about chemical, promising experimental identify new candidates.

Язык: Английский

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Impact of host physiology and external stressors on the bacterial community of Schmidtea mediterranea

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 5, 2025

Abstract To fully comprehend host-microorganism interactions, it is crucial to understand the composition and diversity of microbiome, as well factors that shape these characteristics. We investigated microbiome variation using freshwater planarian Schmidtea mediterranea , an invertebrate model in regeneration biology (eco-)toxicology, by exposing organisms various controlled conditions. The exhibited high variability, with most bacteria belonging Betaproteobacteria. Among diverse microbial communities, a few genera, such Curvibacter were consistently present, but significant alterations response changing relative abundance fluctuated during process, initially increasing before returning similar beginning situation. After applying external stress, other genera decreased. Variation over time, between different origin laboratories individuals, showed additional, yet to-be-identified, are present. Taking all results together, our study provides solid basis for future research focusing on bacterial functionality planarians invertebrates.

Язык: Английский

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map3k1 suppresses terminal differentiation of migratory eye progenitors in planarian regeneration

PLoS Genetics, Год журнала: 2025, Номер 21(3), С. e1011457 - e1011457

Опубликована: Март 17, 2025

Proper stem cell targeting and differentiation is necessary for regeneration to succeed. In organisms capable of whole body regeneration, considerable progress has been made identifying wound signals initiating this process, but the mechanisms that control progenitors into mature organs are not fully understood. Using planarian as a model system, we identify novel function map3k1, MAP3K family member possessing both kinase ubiquitin ligase domains, negatively regulate terminal cells during eye regeneration. Inhibition map3k1 caused formation multiple ectopic eyes within head, without controlling overall brain, or patterning. By contrast, other known regulators patterning like wnt11-6/wntA notum also head regionalization, suggesting acts distinctly. Consistent with these results, resection experiments suggest unlike Wnt signaling perturbation, inhibition did shift target destination in animal. map3k1(RNAi) emerged regions normally occupied by migratory progenitors, animals produced net excess differentiated cells. Furthermore, after coincided an increase numbers cells, decrease ovo+ was preceded prematurely expressing opsin/tyosinase markers differentiation. Therefore, regulates process lineage. Similar phenotypes were observed map2k4, map2k7, jnk, p38 , putative pathway through which prevents Together, results point suppresses their migration destinations.

Язык: Английский

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