Biology subjects

Janssens, D.

Publications and source records attributed to Janssens, D..

5 recordsLinked to original sources

bioRxiv2024

Semaphorin 4A maintains functional diversity of the hematopoietic stem cell pool

Somatic stem cell pools are comprised of diverse, highly specialized subsets whose individual contribution is critical for the overall regenerative function. In the bone marrow, myeloid-biased HSC (myHSC) are indispensable for replenishment of myeloid cells and platelets during inflammatory response but at the same time, become irreversibly damaged during inflammation and aging. Here, we identify an extrinsic factor, Semaphorin 4A (Sema4A), which non cell-autonomously confers myHSC resilience to inflammatory stress. We show that the absence of Sema4A, myHSC inflammatory hyper-responsiveness in young mice drives excessive myHSC expansion, myeloid bias and profound loss of regenerative function with age. Mechanistically, Sema4A is mainly produced by neutrophils, signals via a cell surface receptor Plexin D1 and safeguards myHSC epigenetic state. Our study shows that by selectively protecting a distinct stem cell subset, an extrinsic factor preserves functional diversity of somatic stem cell pool throughout organismal lifespan.

cell biology↗

bioRxiv2022

A wireless, user-friendly, and unattended robotic flower system to assess pollinator foraging behaviour

O_LIUnderstanding the complex interactions between external and internal factors that influence pollinator foraging behaviour is essential for developing effective conservation strategies. However, collecting large datasets that incorporate data from various sources has been challenging. C_LIO_LITo address this issue, we present a wireless and cost-effective robotic flower equipped with Internet of Things (IoT) technology that automatically offers nectar to visiting insects while monitoring visitation time and duration. The robotic flower is easy to manipulate and settings such as nectar refill rates can be remotely altered, making it ideal for field settings. The system transmits data completely wirelessly and autonomously, is mobile and easy to clean. C_LIO_LIThe prototype settings allow for approximately two weeks of uninterrupted data collection for each battery charge. As a proof-of-concept application, a foraging-preference dual choice experiment with bumblebees was performed. On average, more than 14 000 flower visits were registered daily with a setup consisting of 16 robotic flowers. The data show a gradual preference shift from the pre-trained, lower quality food source towards the higher quality source. C_LIO_LIThe robotic flower provides accurate and reliable data on insect behaviour, dramatically reducing the price and/or labour costs. Although primarily designed for (bumble)bees, the system could be easily adapted for other flower-visiting insects. The robotic flower is user-friendly and can be easily adapted to address a wide range of research questions in pollination ecology, conservation biology, biocontrol and ecotoxicology, and allows for detailed studies on how nectar traits, flower colour and shape and pollutants would affect foraging behaviour. C_LI

animal behavior and cognition↗

bioRxiv2020

Automated CUT&Tag profiling of chromatin heterogeneity in mixed-lineage leukemia

Acute myeloid and lymphoid leukemias often harbor chromosomal translocations involving the Mixed Lineage Leukemia-1 gene, encoding the KMT2A lysine methyltransferase. The most common translocations produce in-frame fusions of KMT2A to other chromatin regulatory proteins. Here we develop a strategy to map the genome-wide occupancy of oncogenic KMT2A fusion proteins in primary patient samples regardless of fusion partner. By modifying the versatile CUT&Tag method for full automation we identify common and tumor-specific patterns of aberrant chromatin regulation induced by different KMT2A fusion proteins. Integration of automated and single-cell CUT&Tag uncovers epigenomic heterogeneity within patient samples and predicts sensitivity to therapeutic agents.

genomics↗

bioRxiv2020

Histone deposition pathways determine the chromatin landscapes of H3.1 and H3.3 K27M oncohistones

Lysine 27-to-methionine (K27M) mutations in the H3.1 or H3.3 histone genes are characteristic of pediatric diffuse midline gliomas (DMGs). These oncohistone mutations dominantly inhibit histone H3K27 trimethylation and silencing, but it is unknown how oncohistone type affects gliomagenesis. We show that the genomic distributions of H3.1 and H3.3 oncohistones in human patient-derived DMG cells are consistent with the DNA replication-coupled deposition of histone H3.1 and the predominant replication-independent deposition of histone H3.3. Although H3K27 trimethylation is reduced for both oncohistone types, H3.3K27M-bearing cells retain some domains, and only H3.1K27M-bearing cells lack H3K27 trimethylation. Neither oncohistone interferes with PRC2 binding. Using Drosophila as a model, we demonstrate that inhibition of H3K27 trimethylation occurs only when H3K27M oncohistones are deposited into chromatin and only when expressed in cycling cells. We propose that oncohistones inhibit the H3K27 methyltransferase as chromatin patterns are being duplicated in proliferating cells, predisposing them to tumorigenesis.

molecular biology↗

bioRxiv2019

Max deletion destabilizes MYC protein and abrogates Eμ-Myc lymphomagenesis

Although MAX is widely regarded as an obligate dimerization partner for MYC, its function in normal development and neoplasia is not well defined. We show that B-cell specific deletion of Max has a surprisingly modest effect on B-cell development but completely abrogates E{micro}-Myc driven lymphomagenesis. In both contexts, MAX loss leads to a significant reduction in MYC protein levels. This outcome is associated with the downregulation of numerous transcriptional targets of MAX including a subset that regulate MYC stability. Reduction in MYC protein levels is also observed in multiple cell lines treated with a MYC-MAX dimerization inhibitor. Our work uncovers a layer of Myc autoregulation critical for lymphomagenesis yet partly dispensable for normal lymphoid development.

cancer biology↗