Biology subjects

Hanel, A.

Publications and source records attributed to Hanel, A..

3 recordsLinked to original sources

bioRxiv2025

Hematopoietic proliferation is orchestrated by the sequential and lineage-specific activation of Cyclin D, Cyclin E and CDKN sub-modules within the G1/S network

Commitment to the cell division cycle constrains other fate choices at the single cell level. Hence the molecular network controlling the G1/S transition must be coordinated with developmental phases. Healthy hematopoiesis relies on shifts in cell cycle dynamics that balance proliferation and differentiation of hematopoietic stem cells (HSCs) and lineage progenitors, offering an ideal model system to study the coordination of cell division with development. The G1/S network orchestrates this process by regulating the activites of the master G1/S transcription factors (E2F), and cyclin dependent kinases whose activities drive the progression to S phase. By using single cell transcriptomics profiles of human bone marrow cells and mathematical modeling, we demonstrate that variations in the expression of cyclin D- and cyclin E-centered sub-modules of the G1/S network carve out distinct trajectories from G1 to S, explaining the distinct proliferation properties of hematopoietic cell types evolving in the same microenvironment, and biasing cell fate decisions towards certain lineages. We map 68 hematopoietic cell types to specific model parameters, and identify their individual route through G1/S, using our model. This improved mechanistic understanding of the G1/S transition across cell types could enhance the design of more nuanced pharmacological strategies, enabling more personalized treatment recommendations for current cell cycle-targeted cancer therapies.

systems biology↗

bioRxiv2024

Linker histone H1-0 is a specific mediator of the repressive ETV6::RUNX1 transcriptional landscape

ETV6::RUNX1 is the most common oncogenic fusion in pediatric B cell precursor acute lymphoblastic leukemia (BCP-ALL). It induces a clinically silent preleukemic state that requires secondary mutations for progression to leukemia. However, the molecular mechanisms contributing to the characteristic quiescence of ETV6::RUNX1+ preleukemic cells remain elusive. Here, we detect factors involved in the preleukemic state by generating human induced pluripotent stem cell (hiPSC) models using CRISPR/Cas9 gene editing. We identified upregulation of linker histone H1-0 in our preleukemic models, which was preserved upon hematopoietic differentiation and transformation to BCP-ALL. ETV6::RUNX1 induces H1-0 promoter activity whereas depletion of H1-0 specifically inhibited ETV6::RUNX1 signature genes, indicating its role as a key mediator of the ETV6::RUNX1 transcriptome. Single-cell gene expression analysis revealed high H1-0 levels in quiescent cells during hematopoiesis and inverse correlation with transcriptional activity. Pharmacologically, H1-0 protein levels correspond to susceptibility of BCP-ALL towards histone deacetylase inhibitors (HDACi). Altogether, our study provides novel insights into ETV6::RUNX1-induced quiescence and suggests that further investigation into combinatorial treatment of BCP-ALL using the H1-0- inducing HDACi Quisinostat may be worthwhile.

cancer biology↗

bioRxiv2023

Meta-analysis of herbicide non-target effects on pest natural enemies

A critical component of integrated pest management is minimizing disruption of biological control by reducing use of pesticides with significant non-target effects on natural enemies. Insecticide non-target effects testing for natural enemies has become increasingly common, but research examining the non-target effects of herbicides on natural enemies is scarce and recommendations regarding herbicide selectivity are non-existent. We used meta-analysis to summarize laboratory bioassays testing non-target effects of herbicides on arthropod natural enemies and identify patterns in taxon susceptibility and active ingredient toxicity. Data was extracted from 103 papers representing 801 total observations. Herbicides increased natural enemy mortality and decreased longevity, reproduction, and predation. Mesostigmatan mites and hemipterans were the most sensitive to herbicides and spiders, neuropterans, and hymenopterans were the least sensitive. Mortality was higher in juvenile predators versus parasitoids, but did not differ between adults; parasitoid juveniles are likely better protected within the host. In terms of acute mortality, metribuzin, glufosinate, and oxyfluorfen were the most harmful herbicides. Only nicosulfuron, rimsulfuron, pendimethalin, phenmedipham, atrazine, and urea did not increase natural enemy mortality. The large effect size of glufosinate is particularly concerning, as it is the most likely replacement herbicide for glyphosate in many crops. Many active ingredients remain under-studied. Our analysis indicates that herbicides have a strong potential to disrupt biological control in cropping systems. Simple SummaryReducing the use of pesticides that harm natural enemies of crop pests is important to pest management. Currently, there is limited information on how herbicides might affect natural enemies. The researchers found that herbicides increased natural enemy mortality and reduced their longevity and efficacy as predators. Some potential glyphosate replacement herbicides were more harmful than glyphosate. There was little or no data available for many herbicides and beneficial insects, indicating that much more research is needed on this topic.

ecology↗