Biology subjects

Janssens, C.

Publications and source records attributed to Janssens, C..

4 recordsLinked to original sources

bioRxiv2026

Insecticide resistance of Culex pipiens f. pipiens is geographically widespread in Germany and displays an unmatched genotypic and phenotypic resistance state

In Germany, insecticide use is recommended during mosquito-borne disease outbreaks, yet nationwide data on insecticide resistance in key vector species are scarce. This is particularly relevant for Culex pipiens s.l., a vector of West Nile virus. Here, we provide the first broad-scale assessment of molecular insecticide resistance (kdr and ace-1 mutations) in Cx. pipiens f. pipiens across Germany. We associated insecticide resistances with environmental conditions, potential links with mitochondrial variation of the cytochrome c oxidase I (COI) gene as well as phenotypic resistance (CDC bottle assay with permethrin) of the Frankfurt population with elevated kdr frequencies. Kdr resistance alleles were detected in German Cx. pipiens f. pipiens reaching frequencies of up to 50% in the metropolitan areas of Berlin and Frankfurt am Main. Annual precipitation was negatively associated with kdr allele frequency. Interestingly, ace-1 resistance mutations were only present in the metropolitan area of Frankfurt am Main and in Muggensturm (Rhine valley, southwestern Germany). COI haplotype analyses revealed low genetic variability within German Cx. pipiens f. pipiens populations with no association to the insecticide resistance genotype. Phenotypic assays of the Frankfurt population showed early signs of permethrin resistance, but unmatched genotypic and phenotypic resistance state. This study provides the first broad-scale assessment of molecular insecticide resistance in Cx. pipiens f. pipiens across Germany, establishing a baseline for resistance surveillance and vector control. Further research is needed to identify factors shaping phenotypic resistance, as molecular markers alone may not reliably predict resistance. Since sampling was restricted to urban green spaces, broader sampling across environmental gradients is needed to identify additional environmental effectors.

molecular biology↗

bioRxiv2026

Increases in BCL2L1 and ID1 dosage synergistically drive fate bias and competitive advantage in human pluripotent stem cells

BackgroundGains of chromosome 20q11.21 are among the most common culture-acquired abnormalities in human pluripotent stem cells (hPSC), conferring a well-defined survival advantage while altering differentiation capacity. However, it remains unclear whether this advantage persists during differentiation, how the aneuploidy alters ectodermal and retinal pigment epithelium (RPE) lineage specification, and which genes within the minimal amplicon drive these effects. MethodsWe used three isogenic human embryonic stem cell line pairs (wild-type and 20q11.21 gain) and assessed their behaviour in two neuroectoderm differentiation systems: directed neuroectoderm induction (dual SMAD inhibition) and long-term spontaneous RPE differentiation. Competitive dynamics were measured in mixed cultures, and lineage outcomes were analysed using immunostaining, gene expression profiling and single-cell RNA sequencing. To identify driver genes, we generated BCL2L1 and ID1 overexpression lines and tested their effects under both directed and spontaneous differentiation conditions. ResultsAcross all lines and conditions, 20q cells expanded from a minor fraction to dominate mixed cultures, indicating that their competitive advantage persists beyond the undifferentiated state. Despite this dominance, pure 20q cells failed to specify to neuroectoderm or RPE. Single-cell transcriptomics revealed consistent diversion toward non-neural ectodermal and extraembryonic fates. Mechanistically, overexpression of BCL2L1 and ID1 alone or in combination impaired neuroectoderm specification, while synergistic effect of both genes promoted non-neural ectodermal outcomes under directed differentiation conditions. In spontaneous differentiation, both genes could disrupt differentiation. ConclusionsThe 20q11.21 gain couples a persistent survival advantage with a disruption of neural and RPE lineage competence, redirecting cells toward alternative ectodermal and extraembryonic fates. These effects arise from the combined action of two dosage-sensitive genes BCL2L1 and ID1 within the amplicon, illustrating how regional gene dosage can reshape developmental signalling responses in hPSC.

developmental biology↗

bioRxiv2024

Loss of 18q alters TGFβ signalling affecting anteroposterior neuroectodermal fate in human embryonic stem cells

Chromosomal abnormalities acquired during cell culture can compromise the differentiation potential of human pluripotent stem cells (hPSCs). In this work, we identified a diminished differentiation capacity to retinal progenitor cells in human embryonic stem cells (hESCs) with loss of chromosome 18q. Time-course gene-expression analysis during spontaneous differentiation and single-cell RNA sequencing found that these variant cell lines poorly specified into anterior neuroectoderm, and, when progressing through differentiation, they yielded poorly pigmented cells, with proliferating and pluripotent cell populations. The variant cell lines showed dysregulation of TGF{beta} signaling during differentiation, and chemical modulation of the TGF{beta} pathways showed that the basis of the improper specification was due to imbalances in the anteroposterior neuroectodermal fate commitment.

cell biology↗

bioRxiv2023

SALL3 mediates the loss of neuroectodermal differentiation potential in human embryonic stem cells with chromosome 18q loss

Human pluripotent stem cell (hPSC) cultures are prone to genetic drift, as cells that have acquired specific genetic abnormalities experience a selective advantage in vitro. These abnormalities are highly recurrent in hPSC lines worldwide, but currently their functional consequences in differentiating cells are scarcely described. An accurate assessment of the risk associated with these genetic variants in both research and clinical settings is therefore lacking. In this work, we established that one of these recurrent abnormalities, the loss of chromosome 18q, impairs neuroectoderm commitment and affects the cardiac progenitor differentiation of hESCs. We show that downregulation of SALL3, a gene located in the common 18q loss region, is responsible for failed neuroectodermal differentiation. Knockdown of SALL3 in control lines impaired differentiation in a manner similar to the loss of 18q, while transgenic overexpression of SALL3 in hESCs with 18q loss rescued the differentiation capacity of the cells. Finally, we show by gene expression analysis that loss of 18q and downregulation of SALL3 leads to changes in the expression of genes involved in pathways regulating pluripotency and differentiation, including the WNT, NOTCH, JAK-STAT, TGF-beta and NF-kB pathways, suggesting that these cells are in an altered state of pluripotency.

cell biology↗