Biology subjects

Frasson, C.

Publications and source records attributed to Frasson, C..

3 recordsLinked to original sources

bioRxiv2026

Single-cell multiomic profiling reveals lineage plasticity in pediatric B-lineage Acute Lymphoblastic Leukemia during the early phase of treatment

The biological bases of transient myelomonocytic switch (mmSW) during induction therapy in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) remains largely undefined. Here we integrated single-cell transcriptomic and surface marker profiling with genomic and DNA methylation analyses of pediatric BCP-ALLs, including matched diagnosis (Dx) and Day+15 samples from mmSW-positive (mmSWpos) and mmSW-negative cases. At Dx, mmSWpos leukemia samples were enriched for hematopoietic stem/progenitor-like cell subpopulations. Trajectory and entropy analyses identified a pre-existing "fate-uncertain" cell compartment co-expressing both lymphoid and myeloid programs. Longitudinal single-cell data showed that, in mmSWpos samples, this population undergoes complete transdifferentiation. mmSWpos are enriched for Ras pathway and chromatin regulation mutations and display a specific DNA hypermethylation pattern at Dx. These findings indicate that transient mmSW arises from intrinsic leukemic plasticity, in which immature transcriptomic and distinct epigenetic states at diagnosis enable lineage switching under the pressure of ALL treatment.

Cancer Biology↗

bioRxiv2026

Grass wars: how native and non-indigenous Sporobolus battle heatwaves in salt marshes

O_LIHeatwaves are increasing in frequency and intensity and may alter competitive interactions between native and non-indigenous plant species. C_LIO_LIWe compared the responses of the native Sporobolus maritimus and the non-indigenous Sporobolus anglicus to a simulated 5-day heatwave using an integrative approach combining morphological, physiological, biochemical, transcriptomic, and metabolomic analyses. C_LIO_LIS. maritimus showed reduced survival, greater physiological damage, and no recovery, indicating high sensitivity to heat stress. Conversely, S. anglicus exhibited a rapid and coordinated response, limited damage to the photosynthetic apparatus, and full recovery after stress. C_LIO_LIThese results highlight the greater resilience of S. anglicus and suggest a potential decline of the native species in the Venetian salt marshes under increasing heat stress. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/728445v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@1579ffeorg.highwire.dtl.DTLVardef@1c8e490org.highwire.dtl.DTLVardef@15cbadorg.highwire.dtl.DTLVardef@ef024b_HPS_FORMAT_FIGEXP M_FIG C_FIG We investigated the effects of heatwaves on a native and NIS Sporobolus species from the Venice Lagoon using an integrative, multi-level approach during a simulated 5-day heatwave and recovery phase. The native species showed reduced survival, pronounced physiological damage, and no recovery, indicating high sensitivity to heat stress. Conversely, the NIS exhibited a rapid response, limited impairment of the photosynthetic apparatus, and full recovery. These findings indicate greater resilience of the NIS and suggest a potential decline of the native species in the Venice Lagoon under increasing heat stress. Image created with BioRender (www.biorender.com).

plant biology↗

bioRxiv2026

Selective Disruption of Mutant TP63 Alleles Restores Corneal Epithelial proliferation in EEC Syndrome

Ectrodactyly-Ectodermal Dysplasia-Cleft Lip/Palate (EEC) syndrome is a rare disorder caused by dominant-negative mutations in the TP63 gene, frequently leading to limbal stem cell deficiency (LSCD) and progressive corneal degeneration. Current therapeutic strategies are limited, primarily due to impaired epithelial renewal and poor proliferative capacity of patient-derived cells. We have recently shown that decreasing the expression of the mutated allele by means of siRNA-mediated silencing can restore epithelial cell proliferation. However, the clinical utility of this approach is hindered by the presence of different TP63 mutations causing EEC syndrome, and the need for continuous siRNA administration to achieve sustained gene silencing. To address these challenges, we employed a CRISPR/Cas9-based genome editing strategy to disrupt mutant TP63 alleles in human induced pluripotent stem cells (hiPSCs) derived from EEC patients carrying R279H and R304Q mutations. Targeted editing of exon 6 induced frameshift mutations that activated nonsense-mediated mRNA decay, leading to a significant reduction in mutant transcript levels. Edited hiPSC-derived corneal epithelial cells exhibited improved cell proliferation compared to unedited isogenic controls. These findings demonstrate the feasibility and therapeutic potential of allele-specific genome editing to correct TP63-associated epithelial defects in EEC syndrome paving the way toward future regenerative therapies for TP63-related corneal diseases.

genetics↗