ORCID Profile
0000-0002-8006-0315
Current Organisations
KU Leuven
,
VIB
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Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.NEURON.2012.11.009
Abstract: GABAergic interneurons mainly originate in the medial ganglionic eminence (MGE) of the embryonic ventral telencephalon (VT) and migrate tangentially to the cortex, guided by membrane-bound and secreted factors. We found that Sip1 (Zfhx1b, Zeb2), a transcription factor enriched in migrating cortical interneurons, is required for their proper differentiation and correct guidance. The majority of Sip1 knockout interneurons fail to migrate to the neocortex and stall in the VT. RNA sequencing reveals that Sip1 knockout interneurons do not acquire a fully mature cortical interneuron identity and contain increased levels of the repulsive receptor Unc5b. Focal electroporation of Unc5b-encoding vectors in the MGE of wild-type brain slices disturbs migration to the neocortex, whereas reducing Unc5b levels in Sip1 knockout slices and brains rescues the migration defect. Our results reveal that Sip1, through tuning of Unc5b levels, is essential for cortical interneuron guidance.
Publisher: Springer Science and Business Media LLC
Date: 20-11-2017
DOI: 10.1038/LEU.2017.328
Publisher: Public Library of Science (PLoS)
Date: 27-07-2010
Publisher: The Company of Biologists
Date: 2018
DOI: 10.1242/DEV.157222
Abstract: Upon gastrulation, the mammalian conceptus transforms rapidly from a simple bilayer into a multi-layered embryo enveloped by its extraembryonic membranes. Impaired development of the amnion, the innermost membrane, causes major malformations. To clarify the origin of the mouse amnion, we used single cell-labelling and clonal analysis. We identified four clone types with distinct clonal growth patterns in amniotic ectoderm (AmEc). Two main types have progenitors in extreme proximal-anterior epiblast. Early descendants initiate and expand AmEc posteriorly, while descendants of cells remaining anteriorly later expand AmEc from its anterior side. Amniogenesis is abnormal in embryos deficient in the BMP signalling effector SMAD5, with delayed closure of the proamniotic canal, and aberrant amnion and folding morphogenesis. Transcriptomics of in idual Smad5 mutant amnions isolated before visible malformations, and tetraploid chimera analysis, revealed two amnion defect sets. We attribute them to impairment of progenitors of the two main cell populations in AmEc and to compromised cuboidal-to-squamous transition of anterior AmEc. In both cases, SMAD5 is critical for expanding AmEc rapidly into a stretchable squamous sheet to accommodate exocoelom expansion, axial growth and folding morphogenesis.
Publisher: Ferrata Storti Foundation (Haematologica)
Date: 28-06-2018
Publisher: Elsevier BV
Date: 12-2014
DOI: 10.1016/J.CELREP.2014.11.038
Abstract: Genome control is operated by transcription factors (TFs) controlling their target genes by binding to promoters and enhancers. Conceptually, the interactions between TFs, their binding sites, and their functional targets are represented by gene regulatory networks (GRNs). Deciphering in vivo GRNs underlying organ development in an unbiased genome-wide setting involves identifying both functional TF-gene interactions and physical TF-DNA interactions. To reverse engineer the GRNs of eye development in Drosophila, we performed RNA-seq across 72 genetic perturbations and sorted cell types and inferred a coexpression network. Next, we derived direct TF-DNA interactions using computational motif inference, ultimately connecting 241 TFs to 5,632 direct target genes through 24,926 enhancers. Using this network, we found network motifs, cis-regulatory codes, and regulators of eye development. We validate the predicted target regions of Grainyhead by ChIP-seq and identify this factor as a general cofactor in the eye network, being bound to thousands of nucleosome-free regions.
Publisher: Springer Science and Business Media LLC
Date: 07-07-2017
DOI: 10.1038/S41598-017-04936-7
Abstract: The specification and growth of organs is controlled simultaneously by networks of transcription factors. While the connection between these transcription factors with fate determinants is increasingly clear, how they establish the link with the cell cycle is far less understood. Here we investigate this link in the developing Drosophila eye, where two transcription factors, the MEIS1 homologue hth and the Zn-finger tsh , synergize to stimulate the proliferation of naïve eye progenitors. Experiments combining transcriptomics, open-chromatin profiling, motif analysis and functional assays indicate that these progenitor transcription factors exert a global regulation of the proliferation program. Rather than directly regulating cell cycle genes, they control proliferation through an intermediary layer of nuclear receptors of the ecdysone/estrogen-signaling pathway. This regulatory subnetwork between hth , tsh and nuclear receptors might be conserved from Drosophila to mammals, as we find a significant co-overexpression of their human homologues in specific cancer types.
Publisher: Springer Science and Business Media LLC
Date: 02-04-2019
Publisher: Humana Press
Date: 21-08-2012
DOI: 10.1007/978-1-61779-292-2_18
Abstract: Gene expression regulation is a fundamental biological process leading to complete organism development by controlling processes like cell type specification and differentiation. The accuracy of this process is -governed by transcription factors (TFs) acting within a complex gene regulatory network. CisTargetX has been developed to enable a user to predict TFs, enhancers, and target genes involved in the regulation of co-expressed genes. It uses a strategy that incorporates the genome-wide prediction of clusters of transcription factor binding sites (TFBSs), starting from a large, unbiased collection of position weight matrices (PWMs) and uses comparative genomics criteria to filter potential TFBS. We describe in this chapter, step-by-step, how to use cisTargetX starting from a set of genes or TF(s) to predict transcriptional targets with their putative binding sites and networks in Drosophila. Next, we illustrate this approach on a particular developmental system, namely, sensory organ development, and identify relevant TFs, DNA regions regulating gene expression, and TF/target gene interactions. CisTargetX is available at med.kuleuven.be/lcb/cisTargetX .
Publisher: Oxford University Press (OUP)
Date: 04-05-2015
Publisher: Cold Spring Harbor Laboratory
Date: 15-10-2012
Abstract: The identification of transcription factor binding sites, enhancers, and transcriptional target genes often relies on the integration of gene expression profiling and computational cis -regulatory sequence analysis. Methods for the prediction of cis -regulatory elements can take advantage of comparative genomics to increase signal-to-noise levels. However, gene expression data are usually derived from only one species. Here we investigate tissue-specific cross-species gene expression profiling by high-throughput sequencing, combined with cross-species motif discovery. First, we compared different methods for expression level quantification and cross-species integration using Tag-seq data. Using the optimal pipeline, we derived a set of genes with conserved expression during retinal determination across Drosophila melanogaster , Drosophila yakuba , and Drosophila virilis . These genes are enriched for binding sites of eye-related transcription factors including the zinc-finger Glass, a master regulator of photoreceptor differentiation. Validation of predicted Glass targets using RNA-seq in homozygous glass mutants confirms that the majority of our predictions are expressed downstream from Glass. Finally, we tested nine candidate enhancers by in vivo reporter assays and found eight of them to drive GFP in the eye disc, of which seven colocalize with the Glass protein, namely, scrt , chp , dpr10 , CG6329 , retn , Lim3 , and dmrt99B . In conclusion, we show for the first time the combined use of cross-species expression profiling with cross-species motif discovery as a method to define a core developmental program, and we augment the candidate Glass targetome from a single known target gene, lozenge , to at least 62 conserved transcriptional targets.
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.CELL.2018.06.025
Abstract: Many patients with advanced cancers achieve dramatic responses to a panoply of therapeutics yet retain minimal residual disease (MRD), which ultimately results in relapse. To gain insights into the biology of MRD, we applied single-cell RNA sequencing to malignant cells isolated from BRAF mutant patient-derived xenograft melanoma cohorts exposed to concurrent RAF/MEK-inhibition. We identified distinct drug-tolerant transcriptional states, varying combinations of which co-occurred within MRDs from PDXs and biopsies of patients on treatment. One of these exhibited a neural crest stem cell (NCSC) transcriptional program largely driven by the nuclear receptor RXRG. An RXR antagonist mitigated accumulation of NCSCs in MRD and delayed the development of resistance. These data identify NCSCs as key drivers of resistance and illustrate the therapeutic potential of MRD-directed therapy. They also highlight how gene regulatory network architecture reprogramming may be therapeutically exploited to limit cellular heterogeneity, a key driver of disease progression and therapy resistance.
Publisher: Springer Science and Business Media LLC
Date: 26-05-2020
DOI: 10.1038/S41467-020-16284-8
Abstract: The evolution of winged insects revolutionized terrestrial ecosystems and led to the largest animal radiation on Earth. However, we still have an incomplete picture of the genomic changes that underlay this ersification. Mayflies, as one of the sister groups of all other winged insects, are key to understanding this radiation. Here, we describe the genome of the mayfly Cloeon dipterum and its gene expression throughout its aquatic and aerial life cycle and specific organs. We discover an expansion of odorant-binding-protein genes, some expressed specifically in breathing gills of aquatic nymphs, suggesting a novel sensory role for this organ. In contrast, flying adults use an enlarged opsin set in a sexually dimorphic manner, with some expressed only in males. Finally, we identify a set of wing-associated genes deeply conserved in the pterygote insects and find transcriptomic similarities between gills and wings, suggesting a common genetic program. Globally, this comprehensive genomic and transcriptomic study uncovers the genetic basis of key evolutionary adaptations in mayflies and winged insects.
Publisher: The Company of Biologists
Date: 08-2018
DOI: 10.1242/DEV.169722
Publisher: Public Library of Science (PLoS)
Date: 24-07-2014
No related grants have been discovered for Stein Aerts.