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Évry, France

Onteniente B.,French Institute of Health and Medical Research | Polentes J.,CECS
Cerebrovascular Diseases | Year: 2011

With the development of stem cell (SC) biology, cell-based therapy has become a highly challenging field for experimental and clinical research. Among neurological disorders, stroke has pioneered the clinical application of SC. Safety concerns have prevailed for pilot clinical studies and important preclinical work is ongoing to help SC therapy reach the level of generalization. Stroke is classically divided into an acute, a subacute and a chronic phase. Each phase is defined by a complex array of events with overlapping and distinct kinetics that lead to both rapid tissue degeneration and long-lasting remodeling. Each SC type possesses intrinsic properties - transposed via cell-autonomous and non-cell-autonomous signaling - that would more specifically address some of these events. A better definition of what is expected from SC therapy in stroke might help assign SC sources to the acute or chronic phases and possibly optimize their use in the clinic. Copyright © 2011 S. Karger AG, Basel.

Gauthier M.,French Institute of Health and Medical Research | Maury Y.,CECS | Peschanski M.,French Institute of Health and Medical Research | Martinat C.,French Institute of Health and Medical Research
Regenerative Medicine | Year: 2011

Considerable hope surrounds the use of disease-specific pluripotent stem cells, which can differentiate into any cell type, as starting materials to generate models of human disease that will allow exploration of pathological mechanisms and the search for new treatments. Disease-specific human embryonic stem cells have provided a useful source for studying certain disease states. However, reprogramming of human somatic cells that use readily accessible tissue, such as skin or blood, to generate embryonic-like induced pluripotent stem cells has opened new perspectives for modeling and understanding a larger number of human pathologies. Here, we examine the challenges in creating a disease model from human pluripotent stem cells, and describe their use to model both cell-autonomous and non-cell-autonomous mechanisms, the need for adequate control experiments and the genetic limitations of human induced pluripotent stem cells. Progress in these areas will substantially accelerate effective application of disease-specific human pluripotent stem cells for drug screening. © 2011 Future Medicine Ltd.

Nissan X.,CECS | Blondel S.,French Institute of Health and Medical Research | Peschanski M.,French Institute of Health and Medical Research
Biochemical Society Transactions | Year: 2011

Progeria, also known as HGPS (Hutchinson-Gilford progeria syndrome), is a rare fatal genetic disease characterized by an appearance of accelerated aging in children. This syndrome is typically caused by mutations in codon 608 (C1804T) of the gene encoding lamins A and C, LMNA, leading to the production of a truncated form of the protein called progerin. Owing to their unique potential to self-renew and to differentiate into any cell types of the organism, pluripotent stem cells offer a unique tool to studymolecular and cellular mechanisms related to this global and systemic disease. Recent studies have exploited this potential by generating human induced pluripotent stem cells from HGPS patients' fibroblasts displaying several phenotypic defects characteristic of HGPS such as nuclear abnormalities, progerin expression, altered DNA-repair mechanisms and premature senescence. Altogether, these findings provide new insights on the use of pluripotent stem cells for pathological modelling and may open original therapeutic perspectives for diseases that lack pre-clinical in vitro human models, such as HGPS. ©The Authors Journal compilation ©2011 Biochemical Society.

Zhang D.,CECS | He X.,NICTA | Li H.,NICTA
2014 International Conference on Digital Image Computing: Techniques and Applications, DICTA 2014 | Year: 2015

We present a street scene layout estimation method based on transferring layout annotation from a (large) image database and its application for distant object detection. Inspired by nonparametric scene labeling approaches, we estimate a scene's geometric layout by matching global image descriptors and retrieving the most similar layout configuration. Our label transfer is done for each sub-region of an image and a tiered scene model is used to integrate all the local label information into a coherent scene layout prediction. Given the geometric layout, we use a super-resolution method to zoom in the distance region and refine the search in object detection. On KITTI dataset, we show that we can reliably generate scene layout and improve the detection of distant cars over the state of the art DPM detector. © 2014 IEEE.

Giraud-Triboult K.,CECS | Rochon-Beaucourt C.,French Institute of Health and Medical Research | Nissan X.,CECS | Champon B.,CECS | And 2 more authors.
Physiological Genomics | Year: 2011

Mesenchymal stem cells (MSCs) are present in a wide variety of tissues during development of the human embryo starting as early as the first trimester. Gene expression profiling of these cells has focused primarily on the molecular signs characterizing their potential heterogeneity and their differentiation potential. In contrast, molecular mechanisms participating in the emergence of MSC identity in embryo are still poorly understood. In this study, human embryonic stem cells (hESs) were differentiated toward MSCs (ES-MSCs) to compare the genetic patterns between pluripotent hESs and multipotent MSCs by a large genomewide expression profiling of mRNAs and microRNAs (miRNAs). After whole genome differential transcriptomic analysis, a stringent protocol was used to search for genes differentially expressed between hESs and ES-MSCs, followed by several validation steps to identify the genes most specifically linked to the MSC phenotype. A network was obtained that encompassed 74 genes in 13 interconnected transcriptional systems that are likely to contribute to MSC identity. Pairs of negatively correlated miRNAs and mRNAs, which suggest miRNA-target relationships, were then extracted and validation was sought with the use of Pre-miRs. We report here that underexpression of miR-148a and miR-20b in ES-MSCs, compared with ESs, allows an increase in expression of the EPAS1 (Endothelial PAS domain 1) transcription factor that results in the expression of markers of the MSC phenotype specification. Copyright © 2011 the American Physiological Society.

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