Biomedical subjects

Vincent Frouin

Publications and source records attributed to Vincent Frouin.

9 recordsLinked to original sources

PubMed2021

1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.

Brain↗

PubMed2006

Molecular profile of mouse stromal mesenchymal stem cells.

We determined a transcriptional profile specific for clonal stromal mesenchymal stem cells from adult and fetal hematopoietic sites. To identify mesenchymal stem cell-like stromal cell lines, we evaluated the adipocytic, osteoblastic, chondrocytic, and vascular smooth muscle differentiation potential and also the hematopoietic supportive (stromal) capacity of six mouse stromal cell lines from adult bone marrow and day 14.5 fetal liver. We found that two lines were quadripotent and also supported hematopoiesis, BMC9 from bone marrow and AFT024 from fetal liver. We then ascertained the set of genes differentially expressed in the intersection set of AFT024 and BMC9 compared with those expressed in the union set of two negative control lines, 2018 and BFC012 (both from fetal liver); 346 genes were upregulated and 299 downregulated. Using Ingenuity software, we found two major gene networks with highly significant scores. One network contained downregulated genes that are known to be implicated in osteoblastic differentiation, proliferation, or transformation. The other network contained upregulated genes that belonged to two categories, cytoskeletal genes and genes implicated in the transcriptional machinery. The data extend the concept of stromal mesenchymal stem cells to clonal cell populations derived not only from bone marrow but also from fetal liver. The gene networks described should discriminate this cell type from other types of stem cells and help define the stem cell state.

Animals↗

PubMed2006

Comparison of gene expression pattern in SP cell populations from four tissues to define common "stemness functions".

The goal of our study was to identify a subset of genes commonly expressed in Side Populations (SP), isolated by Hoechst staining followed by flow cytometry, from adult mouse bone marrow, male adult germinal cells, muscle primary culture, and mesenchymal cells. These SP cells have been proposed to be a "stem-like" population and are used here as a "model" that may reveal mechanisms which would be relevant for a better understanding of stem cell properties. Transcriptional profiles for SP and the more differentiated non-SP cells isolated from the four tissues were compared by hybridization on microarray using a common external reference. Among the 503 genes differentially expressed, which discriminate SP and non-SP cells in all the tissues, the genes upregulated in SP cells are implicated in the quiescent status of the cells, the maintenance of their pluripotency and the capacity to undergo asymmetric division. These genes may be responsible for the decision for self-renewal of these cells, whereas the repression of lineage-affiliated genes in SP cells could be responsible for their undifferentiated state. These genes, acting in concert, may be the key players that mediate the mechanisms that control stem cell functions, and our results suggest that we have identified common "stemness functions" of these "stem-like" cells.

Animals↗

PubMed2006

Novel microarray-based method for estimating exposure to ionizing radiation.

Accurate estimation of the dose of ionizing radiation to which individuals have been exposed is critical for therapeutic treatment. We investigated whether gene expression profiles could be used to evaluate the dose received, thereby serving as a biological dosimeter. We used cDNA microarrays to monitor changes in gene expression profiles induced by ionizing radiation in mouse total blood. The subsets of genes best characterizing each dose were identified by resampling the original data set and calculating the intersection of the dose signatures. This analytical strategy minimizes the impact of potential genetic/epigenetic variation between mice and overcomes the bias in gene selection inherent to microarray technology. The significance of the identified signatures was evaluated by monitoring the type I error rate by in silico negative control simulation. Based on the distribution of the mean ratios of the selected probes, we were able to identify transcription profiles giving 83% to 100% correct estimation of the dose received by test mice, demonstrating that the selected probes could be used to determine the dose of radiation to which the animals had been exposed. This method could potentially be generalized to determine the level of exposure to other toxins and could be used to develop new related clinical applications.

Algorithms↗

PubMed2005

Low-dose exposure to gamma rays induces specific gene regulations in normal human keratinocytes.

Skin is the organ most exposed to various environmental aggressors, including ionizing radiation. Low-dose and low-dose-rate exposures to gamma rays account for most occupational, medical or environmental irradiations. To examine whether this type of exposure triggers specific molecular responses, cultured primary keratinocytes isolated from adult normal skin were irradiated with single acute doses of 1 cGy or 2 Gy. DNA microarrays containing 10,500 probes were used to assess transcriptional changes over a time course between 3 and 72 h postirradiation. Keratinocytes were studied at a differentiated stage to mimic the response of cells from the suprabasal layers of the epidermis. A major finding of this study was the identification of an important number of low-dose-specific genes (140), most of which were modulated at 48 h. Clustering analysis also revealed low-dose-specific profiles. One of these clusters (17 known genes) was further analyzed using Gibbs sampling algorithm, which led to the identification of 7 putative promoter sequences. These results show for the first time that low-dose ionizing radiation is able to induce specific transcriptional responses in human keratinocytes. Our findings support the potential usefulness of microarrays in biological dosimetry studies after low-dose exposures.

Cells, Cultured↗

PubMed2005

"Sulcal root" generic model: a hypothesis to overcome the variability of the human cortex folding patterns.

The great variability of cerebral cortical folding patterns raises major problems for the systematic study of functional-structural relationships. This paper describes a novel perspective for explaining this variability, a perspective that relies on gyri buried in the depth of the sulci. From this perspective we propose a generic model of folding, based on indivisible units, called sulcal roots, which correspond to the first folding locations during antenatal life. These units are organized according to a basic scheme allowing us to describe the cortical surface using a system of meridians and parallels. This scheme is thought to be stable across individuals at the fetal stage, and may be related to the protomap model. Variability at the adult stage is thought to result from the chaotic behavior of the folding process: inter-individual differences in cortical areas can lead to qualitatively different folding patterns. We have tested the capacity of this model to match actual cortical anatomy with a database of magnetic resonance images of 20 normal subjects, using new three-dimensional visualization tools giving access to shapes buried in the cortex.

Adult↗

PubMed2003

Striatal neural grafting improves cortical metabolism in Huntington's disease patients.

Huntington's disease is a hereditary disease in which degeneration of neurons in the striatum leads to motor and cognitive deficits. Foetal striatal allografts reverse these deficits in phenotypic models of Huntington's disease developed in primates. A recent open-label pilot study has shown some clinical improvement or stabilization in three out of five Huntington's disease patients who received bilateral striatal grafts of foetal neurons. We show here that the clinical changes in these three patients were associated with a reduction of the striatal and cortical hypometabolism, demonstrating that grafts were able to restore the function of striato-cortical loops. Conversely, in the two patients not improved by the grafts, striatal and cortical hypometabolism progressed over the 2-year follow-up. Finally, detailed anatomical-functional analysis of the grafted striata, enabled by the 3D fusion of MRI and metabolic images, revealed considerable heterogeneity in the anatomic and metabolic profiles of grafted tissue, both within and between Huntington's disease patients. Our results demonstrate the usefulness of PET measurements of brain glucose metabolism in understanding the effects of foetal grafts in patients with Huntington's disease.

Adult↗

PubMed2002

Automatic recognition of cortical sulci of the human brain using a congregation of neural networks.

This paper describes a complete system allowing automatic recognition of the main sulci of the human cortex. This system relies on a preprocessing of magnetic resonance images leading to abstract structural representations of the cortical folding patterns. The representation nodes are cortical folds, which are given a sulcus name by a contextual pattern recognition method. This method can be interpreted as a graph matching approach, which is driven by the minimization of a global function made up of local potentials. Each potential is a measure of the likelihood of the labelling of a restricted area. This potential is given by a multi-layer perceptron trained on a learning database. A base of 26 brains manually labelled by a neuroanatomist is used to validate our approach. The whole system developed for the right hemisphere is made up of 265 neural networks. The mean recognition rate is 86% for the learning base and 76% for a generalization base, which is very satisfying considering the current weak understanding of the variability of the cortical folding patterns.

Artificial Intelligence↗

PubMed2002

Correction of partial-volume effect for PET striatal imaging: fast implementation and study of robustness.

UNLABELLED: PET imaging of D(2) receptors or (18)F-L-dopa metabolism are reference protocols to follow and study neurodegenerative diseases, but the accuracy of striatal PET imaging is limited by the partial-volume effect (PVE). For such studies, the geometric transfer matrix (GTM) method has been proposed to correct the regional mean values for PVE and is now widely used. METHODS: The GTM method models the geometric interactions induced by the PET system between the anatomic regions in which PVE correction is performed. This implies estimation of the corresponding regional spread function (RSF). The literature describes 2 implementations for the RSF calculation; they differ in the way the point spread function (PSF) of the imaging system is modeled, but no comparison or discussion has been given. The first and reference implementation uses an accurate intrinsic detector PSF that is applied in the sinogram space. The second uses a global PSF that is applied in the image space. In this work, we compared the 2 GTM implementations for 3-dimensional (3D) PET striatal imaging using Monte Carlo simulations and a phantom study. We studied the robustness of the GTM correction with respect to residual registration errors between PET and anatomy and with respect to residual segmentation errors. RESULTS: Despite the differences in RSF calculation and computation cost between the 2 implementations, similar recovery results were obtained (between 95% and 100%). The study of robustness of the GTM correction yielded 2 results. A realistic residual misregistration between the anatomic and PET images did not modify the algorithm accuracy but decreased its precision. Conversely, a realistic residual missegmentation of the anatomic regions submitted to GTM correction decreased the correction accuracy. CONCLUSION: A simple but efficient implementation in the image space of the GTM method yields accurate PVE correction in striatal regions in studies with 3D PET and enables clinical use. The method is less sensitive to residual misregistration errors between PET and anatomy than to residual missegmentation of the anatomy. Special care should be taken with segmentation of the regions to correct for PVE.

Corpus Striatum↗