Biology subjects

Cayrac, F.

Publications and source records attributed to Cayrac, F..

4 recordsLinked to original sources

bioRxiv2026

The Pentose Phosphate Pathway Regulates Myelo-Lymphoid Lineage Specification

Following infection, hematopoietic stem and progenitor cells (HSPCs) support immunity by increasing the rate of innate immune cell production but the metabolic cues that guide this process are unknown. To address this question, we combined in situ RNA barcoding and metabolomics approaches to perform metabolic state-fate mapping in vivo. This approach revealed a subset of myeloid-biased HSPCs that express a distinct set of metabolic enzymes and transporters as well as the surface marker CD62L. Metabolically, CD62Lhigh HSPCs have differential activity of the pentose phosphate pathway (PPP), OXPHOS and translation, as well as differential levels of S-adenosylmethionine (SAM) cycle metabolites associated with epigenetic modifications. Inhibition of the PPP skews HSPC lineage fate decisions by disrupting myeloid associated enhancers, while simultaneously increasing enhancer activity for the master B-lymphoid regulator Ikaros. In vivo, overexpression of glucose-6-phosphate dehydrogenase, a rate limiting enzyme of the PPP, skewed HSPC output from B-lymphocytes. In summary, our data shows that HSPCs undergo significant metabolic changes to facilitate the bioenergetic and epigenetic demands of myeloid versus lymphoid lineage specification. We highlight a key role for the pentose phosphate pathway which modulates myeloid rather than lymphoid commitment by shaping the HSPC enhancer landscape, providing proof of principle that HSPC metabolism can be targeted to modulate immune system dynamics.

immunology↗

bioRxiv2025

Shaping and probing living tissues with magnetic bioprinting

Mechanical and geometric cues play a crucial role in vivo, regulating both morphogenetic processes and proper tissue function. This is particularly evident in skeletal muscle, where aligned architecture is essential for myogenesis and functional force generation. However, precisely engineering tissue geometry at both macroscopic and microscopic scales while simultaneously controlling internal mechanical forces remains a significant challenge. In this study, we introduce a magnetic tissue engineering platform based on a magnetic bioprinting technique, enabling precise control of biophysical cues that guide in vitro tissue morphogenesis. Applied here to skeletal muscle, this approach allows for the rapid fabrication of cohesive tissues in any desired shape using cells labeled with magnetic nanoparticles. Additionally, multiple cell types can be incorporated and spatially organized within the same construct through magnetic segregation. Optimizing tissue geometry further enables magnetic actuation, including the ability to trap and maintain tissue shape over time. Furthermore, this magnetic platform facilitates the investigation of how tissue architecture influences mechanical properties, such as resistance to rupture. Overall, this study highlights the significant potential of magnetic bioprinting and stimulation for controlling tissue morphology and advancing biomechanical research.

bioengineering↗

bioRxiv2020

Erythropoietin directly affects single hematopoietic stem cell differentiation after transplantation

The cytokine erythropoietin (EPO) is a potent inducer of erythrocyte development and one of the most prescribed biopharmaceuticals. The action of EPO on erythroid progenitor cells is well established, but its direct action on hematopoietic stem and progenitor cells (HSPCs) is still debated. Here, using cellular barcoding, we traced the differentiation of hundreds of single murine HSPCs, after ex vivo EPO-exposure and transplantation, in five different hematopoietic cell lineages, and observed the transient occurrence of high-output Myeloid-Erythroid-megaKaryocyte (MEK)-biased and Myeloid-B-cell-Dendritic cell (MBDC)-biased clones. Single-cell RNA sequencing (ScRNAseq) analysis of ex vivo EPO-exposed HSPCs revealed that EPO induced the upregulation of erythroid associated genes in a subset of HSPCs, overlapping with multipotent progenitor (MPP) 1 and MPP2. Transplantation of Barcoded EPO-exposed-MPP2 confirmed their enrichment in Myeloid-Erythroid-biased clones. Collectively, our data show that EPO does act directly on MPP independent of the niche, and modulates fate by remodeling the clonal composition of the MPP pool.

immunology↗

bioRxiv2017

Gradients Of Rac1 Nanoclusters Support Spatial Patterns Of Rac1 Signaling

The dynamics of the cytoskeleton and cell shape relies on the coordinated activation of RhoGTPase molecular switches. Among them, Rac1 participates to the orchestration in space and time of actin branching and protrusion/retraction cycles of the lamellipodia at the cell front during mesenchymal migration. Biosensor imaging has revealed a graded concentration of active GTP-loaded Rac1 in protruding regions of the cell. Here, using single molecule imaging and super-resolution microscopy, we reveal an additional supramolecular organization of Rac1. We find that, similarly to H-Ras, Rac1 partitions and is immobilized into nanoclusters of 50-100 molecules each. These nanoclusters assemble due to the interaction of the polybasic tail of Rac1 with the phosphoinositide lipids PIP2 and PIP3. The additional interactions with GEFs, GAPs, downstream effectors, and possibly other partners are responsible for an enrichment of Rac1 nanoclusters in protruding regions of the cell. Using optogenetics and micropatterning tools, we find that activation of Rac1 leads to its immobilization in nanoclusters and that the local level of Rac1 activity matches the local density of nanoclusters. Altogether, our results show that subcellular patterns of Rac1 activity are supported by gradients of signaling nanodomains of heterogeneous molecular composition, which presumably act as discrete signaling platforms. This finding implies that graded distributions of nanoclusters might encode spatial information.\n\nSignificance statementThe plasma membrane of eukaryotic cells is a highly organized surface where hundreds of incoming signals are transduced to the intracellular space. How cells encode faithfully this myriad of signals is a fundamental question. Here we show that Rac1, a critical membrane-bound protein involved in the regulation of cytoskeletal dynamics, forms small aggregates together with other regulating proteins. These supramolecular assemblies, called nanoclusters, are the \"quantal\" units of signaling. By increasing the local concentration, nanoclusters set thresholds for downstream signaling and ensure the fidelity of information transduction. We found that Rac1 nanoclusters are distributed as spatial gradients matching the patterns of Rac1 activity. We propose that cells can encode positional information through distributed signaling quanta, hereby ensuring spatial fidelity.

biophysics↗