Biology subjects

Manchon, L.

Publications and source records attributed to Manchon, L..

3 recordsLinked to original sources

bioRxiv2025

Temporal dynamics of macrophages transcriptional profiles during zebrafish wound healing

Macrophages participate to wound healing by contributing to host defense and orchestrating inflammation and repair. They adapt dynamically to the wound microenvironment by adopting diverse polarization states, which are determinant of wound outcome, influencing whether healing is successful or becomes chronic. The zebrafish embryo, widely used for live imaging of immune responses, is a powerful model to study macrophage behavior after injury. However, the transcriptional landscape of polarized macrophages in this model during wound healing remains insufficiently characterized. Here, we employ bulk RNA sequencing to characterize macrophage transcriptional programs following tail fin wounding a robust model for studying sterile inflammation. Our findings reveal that zebrafish macrophages undergo large transcriptomic changes along different wound healing phases, particularly between 2 and 5 hours post-amputation, suggesting a fast reprogramming leading to different functional states. We further show that, at 2h, macrophages acquire a pro-inflammatory profile with a gene signature closed to M1 signature. At 5h, macrophages express genes involved in immunoregulation and healing associated with shutoff of pro-inflammatory pathways and the activation of glucose and glycogen metabolism. Finally, we show that macrophage reprogramming becomes deeply attenuated by 29h. Our findings provide a foundation for understanding macrophage polarization in zebrafish, revealing underpinning molecular mechanisms, including both specific and evolutionarily conserved pathways with a potential impact on translational medicine.

immunology↗

bioRxiv2019

Modulation of Yorkie activity by alternative splicing is required for developmental stability

The mechanisms that contribute to developmental stability are barely known. Here we show that alternative splicing of yorkie (yki) is required for developmental stability in Drosophila. Yki encodes the effector of the Hippo pathway that has a central role in controlling organ growth and regeneration. We identify the splicing factor B52 as necessary for inclusion of yki alternative exon 3 that encodes one of the two WW domains of Yki protein. B52 depletion favors expression of Yki1 isoform carrying a single WW domain, and reduces growth in part through modulation of yki alternative splicing. Compared to the canonical Yki2 isoform containing two WW domains, Yki1 isoform has reduced transcriptional and growth-promoting activities, decreased binding to PPxY-containing partners, and lacks the ability to bridge two proteins containing PPxY motifs. Yet, Yki1 and Yki2 interact similarly with transcription factors and can thus compete in vivo. Strikingly, flies deprived from Yki1 isoform exhibit increased fluctuating wing asymmetry, a signal of increased developmental noise. Our results identify yki alternative splicing as a new level of control of the Hippo pathway and provide the first experimental evidence that alternative splicing participates in developmental robustness.

developmental biology↗

bioRxiv2019

Targeting the Long Non-Coding RNA LINC00599-205 splicing by novel candidate drug ABX464 to produce anti-inflammatory MicroRNA miR-124

Many nascent long non-coding RNAs have received considerable attention in recent years because of their major regulatory roles in gene expression and signaling pathways at various levels. Indeed long non-coding RNAs undergo the same maturation steps as pre-mRNAs of proteincoding genes, but they are less efficiently spliced and polyadenylated in comparison to them. Here we focus on a specific human long non-coding RNA and we show the activity of a new candidate drug that potentially affect its splicing and generate an anti-HIV and anti-inflammatory effects driven by upregulation of microRNA biogenesis. To investigate this activity we combine the use of capture sequencing technology and an ab initio transcript assembly on cells from six healthy individuals. The sequencing depth of capture sequencing permitted us to assemble transcripts exhibiting a complex array of splicing patterns. In essence, we revealed that splicing of the long non-coding RNA is activated by the drug whereas this splicing was not present in untreated samples.

immunology↗