Biology subjects

Renaud, S.

Publications and source records attributed to Renaud, S..

5 recordsLinked to original sources

bioRxiv2026

Pancreatic α-cells are required for nutrient homeostasis by regulating dynamic β-cell networks in islets

Pancreatic islets contain -, {beta}-, {gamma}- and {delta}-cells as sensors and actuators regulating glucose homeostasis. Despite the known importance of -cells, they are seemingly required for glucose tolerance only under metabolic stress. In an inducible model of -cell ablation in mice (GluDTR), glucose tolerance was considerably decreased by physiological addition of amino-acids mimicking meals. Analysis of islet {beta}-cell secretion and electrical activities using microelectrode arrays (MEA) detected only minor differences in GluDTR mice for glucose but revealed a major reduction upon addition of amino acids. Analysis of functional islet {beta}-cell networks by high density MEA revealed leading regions in different locations, a high degree of synchrony and the activation of large cell clusters. The characteristics of leading regions were preserved in GluDTR islets, but synchrony, cluster size and signal propagation speed were largely reduced. Thus, even without metabolic stress, -cells are required for nutrient homeostasis by regulating the dynamics of {beta}-cell networks. TeaserIslet -cells are required for meal tolerance by adjusting synchrony, cluster size and signal propagation of {beta}-cell networks.

physiology↗

bioRxiv2024

Hypoxia and loss of GCM1 expression prevents differentiation and contact inhibition in human trophoblast stem cells

The placenta develops alongside the embryo and nurtures fetal development to term. During the first stages of embryonic development, due to low blood circulation, the blood and ambient oxygen supply is very low ([~]1-2% O2) and gradually increases upon placental invasion. While a hypoxic environment is associated with stem cell self-renewal and proliferation, persistent hypoxia may have severe effects on differentiating cells and could be the underlying cause of placental disorders. We find that human trophoblast stem cells (hTSC) thrive in low oxygen, whereas differentiation of hTSC to trophoblast to syncytiotrophoblast (STB) and extravillous trophoblast (EVT) is negatively affected by hypoxic conditions. The pro-differentiation factor GCM1 (human Glial Cell Missing-1) is downregulated in low oxygen, and concordantly there is substantial reduction of GCM1-regulated genes in hypoxic conditions. Knockout of GCM1 in hTSC caused impaired EVT and STB formation and function, reduced expression of differentiation-responsive genes, and resulted in maintenance of self-renewal genes. Treatment with a PI3K inhibitor reported to reduce GCM1 protein levels likewise counteracts spontaneous or directed differentiation. Additionally, chromatin immunoprecipitation of GCM1 showed enrichment of GCM1-specific binding near key transcription factors upregulated upon differentiation including the contact inhibition factor CDKN1C. Loss of GCM1 resulted in downregulation of CDKN1C and corresponding loss of contact inhibition, implicating GCM1 in regulation of this critical process.

cell biology↗

bioRxiv2024

Continuous monitoring of glucose levels in vivo with a micro-organ based microfluidic biosensor

Continuous monitoring of glucose levels has improved diabetes therapy. Current approaches rely on enzyme-linked electrochemical probes but do not allow a fully autonomous artificial pancreas. In contrast, monitoring the activity of a few electrogenic pancreatic islets in a biosensor may harness the computational power of the different endocrine cell types in the micro-organ, shaped for nutrient detection during evolution, and provide a more appropriate read-out. Extracellular electrophysiology captures slow potentials (SPs), which reflect coupled islet {beta}-cell activity and is thus a method of choice for long-term monitoring of native islet activity in vitro. We have now developed a microfluidic microelectrode chip containing a few islets and linked to interstitial fluids in live rats by subcutaneous microdialysis. The electrical activity in terms of slow potentials monitored by this biosensor reacts ex vivo proportionally to glucose levels off-line in serum or dialysed interstitial fluid. On-line monitoring in vivo reveals an excellent correlation between islet slow potential frequency, and to a lesser degree to slow potential amplitudes, to glucose concentrations with little variation between animals. The microorgan-based biosensor harness multiple parameters in vivo and provides a read-out closer to physiology. This demonstrates the usefulness of such biosensors for sensor-based therapy of diabetes.

physiology↗

bioRxiv2020

Deep learning for species identification of modern and fossil rodent molars

Reliable identification of species is a key step to assess biodiversity. In fossil and archaeological contexts, genetic identifications remain often difficult or even impossible and morphological criteria are the only window on past biodiversity. Methods of numerical taxonomy based on geometric morphometric provide reliable identifications at the specific and even intraspecific levels, but they remain relatively time consuming and require expertise on the group under study. Here, we explore an alternative based on computer vision and machine learning. The identification of three rodent species based on pictures of their molar tooth row constituted the case study. We focused on the first upper molar in order to transfer the model elaborated on modern, genetically identified specimens to isolated fossil teeth. A pipeline based on deep neural network automatically cropped the first molar from the pictures, and returned a prediction regarding species identification. The deep-learning approach performed equally good as geometric morphometrics and, provided an extensive reference dataset including fossil teeth, it was able to successfully identify teeth from an archaeological deposit that was not included in the training dataset. This is a proof-of-concept that such methods could allow fast and reliable identification of extensive amounts of fossil remains, often left unstudied in archaeological deposits for lack of time and expertise. Deep-learning methods may thus allow new insights on the biodiversity dynamics across the last 10.000 years, including the role of humans in extinction or recent evolution.

zoology↗

bioRxiv2018

Restoring ventilatory control using an adaptive bioelectronic system

Key Points SummaryO_LIElectrical stimulation of the diaphragm muscle or phrenic nerve, or ventilatory pacing, serves as an alternative to mechanical ventilation.\nC_LIO_LICurrently available ventilatory pacing systems are open-loop, requiring long set-up sessions and frequent tuning.\nC_LIO_LIA neuromorphic closed-loop bioelectronic controller capable of autonomously adapting current amplitude to achieve a desired breath volume profile has been developed.\nC_LIO_LIThe controller was able to achieve a desired volume profile in intact animals and restore tidal volume to values observed prior to injury in spinal cord hemisected animals.\nC_LIO_LIThis controller architecture allows for ventilatory pacing that requires minimal technician input during setup and constantly adapts to account for changes such as those induced by muscle fatigue.\nC_LIO_LIThe adaptive control system could be used as a respiratory rehabilitation tool to strengthen inspiratory muscles and for automated weaning from mechanical ventilation.\nC_LI\n\nAbstractVentilatory pacing via electrical stimulation of the phrenic nerve or of the diaphragm has been shown to enhance quality of life compared to mechanical ventilation. However, commercially-available ventilatory pacing devices require initial manual specification of stimulation parameters and frequent adjustment to achieve and maintain suitable ventilation over long periods of time. Here, we have developed an adaptive, closed-loop, neuromorphic, pattern-shaping controller capable of automatically determining a suitable stimulation pattern and adapting it to maintain a desired breath volume profile on a breath-by-breath basis. In vivo studies in anesthetized intact and C2-hemisected male Sprague-Dawley rats indicated that the controller was capable of automatically adapting stimulation parameters to attain a desired volume profile. Despite diaphragm hemiparesis, the controller was able to achieve a desired volume in the injured animals that did not differ from the tidal volume observed prior to injury (p=0.39). The closed-loop controller was developed and parametrized in a computational testbed prior to in-vivo assessment. This bioelectronic technology could serve as an individualized and autonomous respiratory pacing approach for support or recovery from ventilatory deficiency.

physiology↗