Christophe Antoniewski

• PhD
• Head of Department at Institut de Biologie Paris Seine

Studying ciliary genes in the context of the human central nervous system is crucial for understanding the underlying causes of neurodevelopmental ciliopathies. Here, we use pluripotent stem cell-derived spinal organoids to reveal distinct functions of the ciliopathy gene RPGRIP1L in humans and mice, and uncover an unexplored role for cilia in huma...

T-cell acute lymphoblastic leukemia (T-ALL) is a hematopoietic malignancy characterized by increased proliferation and incomplete maturation of T-cell progenitors, for which relapse is often of poor prognosis. To improve patient outcomes, it is critical to understand the chemoresistance mechanisms arising from cell plasticity induced by the bone ma...

The lateral wall of the mouse subventricular zone harbors neural stem cells (NSC, B cells) which generate proliferating transient-amplifying progenitors (TAP, C cells) that ultimately give rise to neuroblasts (NB, A cells). Molecular profiling at the single-cell level struggles to distinguish these different cell types. Here, we combined transcript...

Deciphering shared features between patients through unsupervised analyses of tumor single-cell transcriptomes is hindered by the predominant clustering of malignant cells based on the patient's tumor of origin. In contrast, cancer-associated non-malignant cells within tumors cluster according to their somatic cell type (e.g. macrophage, fibroblast...

Germline cells produce gametes, which are specialized cells essential for sexual reproduction. Germline cells first amplify through several rounds of mitosis before switching to the meiotic program, which requires specific sets of proteins for DNA recombination, chromosome pairing, and segregation. Surprisingly, we previously found that some protei...

Germline cells produce gametes, which are specialized cells essential for sexual reproduction. Germline cells first amplify through several rounds of mitosis before switching to the meiotic program, which requires specific sets of proteins for DNA recombination, chromosome pairing and segregation. Surprisingly, we previously found that some protein...

The lateral wall of the subventricular zone harbors neural stem cells (NSC, B cells) which generate proliferating transient-amplifying progenitors (TAP, C cells) that ultimately give rise to neuroblasts (NB, A cells). Molecular profiling at the single cell level struggles to distinguish these different cell types. Here, we combined transcriptome an...

T-cell acute lymphoblastic leukemia (T-ALL) is a hematopoietic malignancy characterized by an increased proliferation and incomplete maturation of T-cell progenitors. Despite therapeutic improvements, relapses are often of bad prognosis. Therapeutic vulnerabilities and chemoresistance mechanisms arising from cell plasticity induced by the bone marr...

Ageing is characterised at the molecular level by six transcriptional ‘hallmarks of ageing’, that are commonly described as progressively affected as time passes. By contrast, the ‘Smurf’ assay separates high‐and‐constant‐mortality risk individuals from healthy, zero‐mortality risk individuals, based on increased intestinal permeability. Performing...

The lateral wall of the subventricular zone harbors neural stem cells (NSC, B cells) which generate proliferating transient-amplifying progenitors (TAP, C cells) that ultimately give rise to neuroblasts (NB, A cells). Molecular profiling at the single cell level struggles to distinguish these different cell types. Here, we combined transcriptome an...

The lateral wall of the subventricular zone harbors neural stem cells (NSC, B cells) which generate proliferating transient-amplifying progenitors (TAP, C cells) that ultimately give rise to neuroblasts (NB, A cells). Molecular profiling at the single cell level struggles to distinguish these different cell types. Here, we combined transcriptome an...

The lateral wall of the subventricular zone harbors neural stem cells (NSC, B cells) which generate proliferating transient-amplifying progenitors (TAP, C cells) that ultimately give rise to neuroblasts (NB, A cells). Molecular profiling at the single cell level struggles to distinguish these different cell types. Here, we combined transcriptome an...

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, yet it remains refractory to systemic therapy. Elimination of senescent cells has emerged as a promising new treatment approach against cancer. Here, we investigated the contribution of senescent cells to GBM progression. Senescent cells are identified in patient and mou...

Ageing is a common feature of living organisms, showing shared molecular features called hallmarks of ageing. Usually they are quantified in groups of individuals as a function of their chronological age (time passed since birth) and display continuous and progressive changes. Such approaches are based on the assumption that individuals taken at a...

Cell motility is critical for tumor malignancy. Metabolism being an obligatory step in shaping cell behavior, we looked for metabolic weaknesses shared by motile cells across the diverse genetic contexts of patients' glioblastoma. Computational analyses of single-cell transcriptomes from thirty patients' tumors isolated cells with high motile poten...

Cells remodel their cytoplasm with force-generating cytoskeletal motors. Their activity generates random forces that stir the cytoplasm, agitating and displacing membrane-bound organelles like the nucleus in somatic and germ cells. These forces are transmitted inside the nucleus, yet their consequences on liquid-like biomolecular condensates residi...

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, yet it remains refractory to systemic therapy. Elimination of senescent cells has emerged as a promising new treatment approach against cancer. Here, we investigated the contribution of senescent cells to GBM progression. Senescent cells were identified in patient and mo...

Cancer cells in similar functional states are found in all glioblastoma, despite the genomic heterogeneity observed between and within these brain tumors. Metabolism being downstream of all signaling pathways regulating cell behaviors, we looked for metabolic weaknesses in link with motility, a key functional state for glioblastoma aggressiveness....

Introduction Fanconi anemia (FA) is the most frequent inherited DNA-repair disease in human, driving hematopoietic stem cell (HSC) failure in children and a major predisposition to poor-prognosis myelodysplastic syndrome (MDS) and acute leukemia (AML) in children or young adults. MDS/AML secondary to FA have a dismal prognosis in this frail populat...

Background The vast ecosystem of single-cell RNA-sequencing tools has until recently been plagued by an excess of diverging analysis strategies, inconsistent file formats, and compatibility issues between different software suites. The uptake of 10x Genomics datasets has begun to calm this diversity, and the bioinformatics community leans once more...

tRNA fragments (tRFs) are a class of small non-coding RNAs (sncRNAs) derived from tRNAs. tRFs are highly abundant in many cell types including stem cells and cancer cells, and are found in all domains of life. Beyond translation control, tRFs have several functions ranging from transposon silencing to cell proliferation control. However, the analys...

Background The vast ecosystem of single-cell RNA-seq tools has until recently been plagued by an excess of diverging analysis strategies, inconsistent file formats, and compatibility issues between different software suites. The uptake of 10x Genomics datasets has begun to calm this diversity, and the bioinformatics community leans once more toward...

2-O-Methylation (Nm) represents one of the most common RNA modifications. Nm affects RNA structure and function with crucial roles in various RNA-mediated processes ranging from RNA silencing, translation, self versus non-self recognition to viral defense mechanisms. Here, we identify two Nm methyltransferases (Nm-MTases) in Drosophila melanogaster...

mRNA translation and decay appear often intimately linked although the rules of this interplay are poorly understood. In this study, we combined our recent P-body transcriptome with transcriptomes obtained following silencing of broadly acting mRNA decay and repression factors, and with available CLIP and related data. This revealed the central rol...

tRNA fragments (tRFs) are a class of small non-coding RNAs (sncRNAs) derived from tRNAs. tRFs are highly abundant in many cell types including stem cells and cancer cells, and are found in all domains of life. Beyond translation control, tRFs have several functions ranging from transposon silencing to cell proliferation control. However, the analys...

Glioblastoma cell ability to adapt their functioning to microenvironment changes is a source of the extensive intra-tumor heterogeneity characteristic of this devastating malignant brain tumor. A systemic view of the metabolic pathways underlying glioblastoma cell functioning states is lacking. We analyzed public single cell RNA-sequencing data fro...

Glioblastoma cell ability to adapt their functioning to microenvironment changes is a source of the extensive intra-tumor heterogeneity characteristic of this devastating malignant brain tumor. A systemic view of the metabolic pathways underlying glioblastoma cell functioning states is lacking. We analyzed public single cell RNA-sequencing data fro...

2-O-methylation (Nm) represents one of the most common RNA modifications. Nm affects RNA structure and function with crucial roles in various RNA-mediated processes ranging from RNA silencing, translation, self versus non-self recognition to viral defense mechanisms. Here, we identify two novel Nm methyltransferases (Nm-MTases) in Drosophila melano...

piRNA-mediated repression of transposable elements (TE) in the germline limits the accumulation of mutations caused by their transposition. It is not clear whether the piRNA pathway plays a role in adult, nongonadal tissues in Drosophila mel-anogaster. To address this question, we analyzed the small RNA content of adult Drosophila melanogaster head...

piRNA-mediated repression of transposable elements (TE) in the germline limits the accumulation of heritable mutations caused by their transposition in the genome. It is not clear whether the piRNA pathway plays a functional role in adult, non-gonadal tissues in Drosophila melanogaster. To address this question, we first analyzed the small RNA cont...

The control of protein expression results from the fine tuning of mRNA synthesis, decay and translation. These processes, which are controlled by a large number of RNA binding proteins and by localization in RNP granules such as P-bodies, appear often intimately linked although the rules of this interplay are not well understood. In this study, we...

piRNA-mediated repression of transposable elements (TE) in the germline limits the accumulation of heritable mutations caused by their transposition in the genome. It is not clear whether the piRNA pathway plays a functional role in adult, non-gonadal tissues in Drosophila melanogaster . To address this question, we first analyzed the small RNA con...

Skeletal muscle satellite cells are quiescent adult resident stem cells that activate, proliferate and differentiate to generate myofibres following injury. They harbour a robust proliferation potential and self-renewing capacity enabling lifelong muscle regeneration. Although several classes of microRNAs were shown to regulate adult myogenesis, sy...

Metavisitor is a software package that allows biologists and clinicians without specialized bioinformatics expertise to detect and assemble viral genomes from deep sequence datasets. The package is composed of a set of modular bioinformatic tools and workflows that are implemented in the Galaxy framework. Using the graphical Galaxy workflow editor,...

Screenshot of Metavisitor workflow for Use Case 1–2. (PDF)

Alignments of small RNA sequence reads to the partially reconstructed Anopheles C virus genome (Use Case 2–1). Plot shows the abundance of 18–30-nucleotide (nt) small RNA sequence reads matching the genome sequences and histogram shows length distributions of these reads. Positive and negative values correspond to sense and antisense reads, respect...

Screenshot of Metavisitor workflow for remapping in use cases 2–1 and 2–2. (PDF)

Screenshot of Metavisitor workflow for Use Case 3–2. (PDF)

Screenshot of Metavisitor workflow for Use Case 3–3. (PDF)

Nora_MV sequence of Nora virus reconstructed by Metavisitor using reads collapsed to unique sequences (Use Case 1–1). (TXT)

MAFFT (http://www.ebi.ac.uk/Tools/msa/mafft/) Multiple Alignment of the Nora virus genome sequences published (JX220408.1 and NC_007919.3) or generated in Use Cases 1-1 to 1-3 (Nora_MV, Nora_raw_reads and Nora_Median−Norm−reads). A view of the alignments was produced by MView (http://www.ebi.ac.uk/Tools/msa/mview/). The html file can be visualized...

Screenshot of the “Retrieve FASTA from NCBI” tool form to retrieve viral nucleotide (A) or protein (B) vir1 sequences. The query string “txid10239[orgn] NOT txid131567[orgn] NOT phage” retrieves viruses sequences (txid10239) while filtering out cellular organisms sequences (txid131567) and phage sequences. (PDF)

Screenshot of an output produced by the “Parse blast output and compile hits” Metavisitor tool. (PDF)

Screenshot of Metavisitor workflow for Use Case 1–3. (PDF)

Screenshot of Metavisitor workflow for Use Case 1–4. (PDF)

Screenshot of Metavisitor workflow for Use Case 2–2. (PDF)

Screenshot of Metavisitor workflow for Trinity test in Use Case 2–2. (PDF)

Screenshot of Metavisitor workflow for SPAdes test in Use Case 2–2. (PDF)

Screenshot of Metavisitor workflow for Use Case 3–1. (PDF)

Nora_raw_reads sequence of Nora virus reconstructed by Metavisitor using raw reads (Use Case 1–2). (TXT)

Nora_Median-Norm-reads sequence of Nora virus reconstructed by Metavisitor using normalisation of read abundance by median procedure (Use Case 1–3). (TXT)

Output of the “parse blast output and compile hits” tool in Use Case 1–4. (TXT)

Output of the “parse blast output and compile hits” tool in Use Case 2–1. (TXT)

Output of the “Pick Fasta Sequences” tool in Use Case 2–1. (TXT)

Sequences of the 4 contigs generated by the “CAP3 sequence assembly” tool in Use Case 2–1. (TXT)

Merge of all reports generated by the “Parse blast output and compile hits” tool in Use Case 3–2. These reports are summarized in Table 3. (TXT)

Ebola virus reconstructed sequences in NC_002549.1 scaffold in Use Case 3–3. (TXT)

Sequence-independent strategy to identify candidate viral contigs (Use Case 2–1). Set of contigs (Loci) with clear (+), unclear (?) or no siRNA signature were manually selected from S10 Fig and tested for significant blastx alignment against the vir1 index and the Non-redundant NCBI protein database (october 201). (PDF)

Screenshot of Metavisitor workflow for Use Case 1-1. (PDF)

Screenshot of Metavisitor workflow for remapping for use cases 1–1, 1–2, 1–3. (PDF)

Screenshot of Metavisitor workflow for small RNA profiling of contigs. (PDF)

Parsing of blastx alignments with the “blast analysis, by subjects” tool in Use Case 2–2. (TXT)

Merge of all reports for Ebola virus generated by the “Parse blast output and compile hits” tool in Use Case 3–3. These reports are summarized in Table 4. (TXT)

Lassa virus segment L reconstructed sequences in NC_004297.1 scaffold in Use Case 3–3. (TXT)

Galaxy tools used in Metavisitor. (PDF)

Screenshot of Metavisitor workflow for Use Case 2–1. (PDF)

siRNA profiling of de novo assembled contigs in Use Case 2–1. Small RNA sequences reads were aligned to the contigs and size distribution and read maps were generated using the “Generate readmap and histograms from alignment files” tool. Plots show the map and abundance of 18–30 nt small RNA reads for indicated contigs and histograms show length di...

Merge of all reports for Lassa virus generated by the “Parse blast output and compile hits” tool in Use Case 3–3. These reports are summarized in Table 4. (TXT)

Lassa virus segment S reconstructed sequences in NC_004296.1 scaffold in Use Case 3–3. (TXT)

Integration of the 4 assembled contigs (S8 File) in the DCV genome scaffold NC_001834.1 by the “blast_to_scaffold” tool. Lowercase correspond to NC_001834.1 sequences while uppercase correspond to contig sequences. (TXT)

Sequence of the 8919 nt contig in Use Case 2–2. (TXT)

MAFFT (http://www.ebi.ac.uk/Tools/msa/mafft/) Multiple Alignment in Clustal format of 3 AnCV genomes reconstructed with Oases, Trinity and SPAdes assembly programs. (TXT)

Merge of all reports generated by the “Parse blast output and compile hits” tool in Use Case 3–1. (TXT)

Duration of execution of the Metavisitor workflows. The times given correspond to execution of the workflows on a 16-core (2GHz) machine with 96 Mo RAM, Galaxy release 16.04. (PDF)

We present user-friendly and adaptable software to provide biologists, clinical researchers and possibly diagnostic clinicians with the ability to robustly detect and reconstruct viral genomes from complex deep sequence datasets. A set of modular bioinformatic tools and workflows was implemented as the Metavisitor package in the Galaxy framework. U...

Mosquitoes of the Anopheles gambiae complex display strong preference for human bloodmeals and are major malaria vectors in Africa. However, their interaction with viruses or role in arbovirus transmission during epidemics has been little examined, with the exception of O’nyong-nyong virus, closely related to Chikungunya virus. Deep-sequencing has...

Transposable element (TE) activity is repressed in the germline in animals by PIWI-Interacting RNAs (piRNAs), a class of small RNAs produced by genomic loci mostly composed of TE sequences. The mechanism of induction of piRNA production by these loci is still enigmatic. We have shown that, in Drosophila melanogaster, a cluster of tandemly repeated...

RNase P is a conserved endonuclease that processes the 5' trailer of tRNA precursors. We have isolated mutations in Rpp30, a subunit of RNase P, and find that these induce complete sterility in Drosophila females. Here, we show that sterility is not due to a shortage of mature tRNAs, but that atrophied ovaries result from the activation of several...

Small RNAs are potent regulators of gene expression. They also act in defense pathways against invading nucleic acids such as transposable elements or viruses. To counteract these defenses, viruses have evolved viral suppressors of RNA silencing (VSRs). Plant viruses encoded VSRs interfere with siRNAs or miRNAs by targeting common mediators of thes...

The optimal coordination of the transcriptional response of host cells to infection is essential for establishing appropriate immunological outcomes. In this context, the role of microRNAs (miRNAs) - important epigenetic regulators of gene expression - in regulating mammalian immune systems is increasingly well recognised. However, the expression d...

Significance It is important to understand antiviral mechanisms in potential new arbovirus vectors, such as Anopheles mosquitoes, in order to assess risks associated with arbovirus spread. Using an arbovirus naturally transmitted by Anopheles , we find that important immune mechanisms involved in the first bottleneck to Anopheles infection, the mid...

High-throughput sequencing approaches opened the possibility to precisely map full populations of small RNAs to the genomic loci from which they originate. A bioinformatic approach revealed a strong tendency of sense and antisense piRNAs to overlap with each other over ten nucleotides and had a major role in understanding the mechanisms of piRNA bi...

The tombusvirus P19 VSR (viral suppressor of RNA interference) binds siRNAs with high affinity, whereas the Flockhouse Virus (FHV) B2 VSR binds both long double-stranded RNA (dsRNA) and small interfering RNAs (siRNAs). Both VSRs are small proteins and function in plant and animal cells. Fusing a Nuclear Localization Signal (NLS) to the N-terminus s...

Transposable element (TE) activity is repressed in the Drosophila germline by Piwi-Interacting RNAs (piRNAs), a class of small non-coding RNAs. These piRNAs are produced by discrete genomic loci containing TE fragments. In a recent publication, we tested for the existence of a strict epigenetic induction of piRNA production capacity by a locus in t...

Defects in miRNA biogenesis or activity are associated to development abnormalities and diseases. In Drosophila, miRNAs are predominantly loaded in Argonaute-1, which they guide for silencing of target RNAs. The miRNA pathway overlaps the RNAi pathway in this organism, as miRNAs may also associate with Argonaute-2, the mediator of RNAi. We set up a...

List of selected compounds. The compounds were clustered in 22 structural families (A to V) using the Tanimoto coefficient and the K-modes procedure. Compounds selected for further validation are enlightened in orange. Shaded compounds were discarded as false positives after microscopy analysis because they emit diffuse fluorescence in the culture...

Abundances of miRNA sequencing reads in small RNA libraries from automiG S2R+ cells and from ubi-automiG transgenic adult flies. miG-1 and miG-2 are orange shaded. mir-5 and mir-6.1 are light-blue shaded. Note that the mir-5/mir-6 cluster is mostly expressed during embryogenesis and that only very few reads matching these miRNAs are recovered from...

Piwi-interacting RNAs (piRNAs) ensure transposable element silencing in Drosophila, thereby preserving genome integrity across generations. Primary piRNAs arise from the processing of long RNA transcripts produced in the germ line by a limited number of telomeric and pericentromeric loci. Primary piRNAs bound to the Argonaute protein Aubergine then...

Late onset neurodegenerative diseases represent a major public health concern as the population in many countries ages. Both frequent diseases such as Alzheimer disease (AD, 14% incidence for 80–84 year-old Europeans) or Parkinson disease (PD, 1.4% prevalence for >55 years old) share, with other low-incidence neurodegenerative pathologies such as s...

Analysis of miRNAs expression in fly heads in independent experiments. Deep sequencing was performed on age matched whole male flies with the same experimental methods than with fly heads. Raw data for body and head samples are provided in the first sheet. Normalized data including this experiment and data from (Chung et al., 2008; Exp2), and (Bere...