Yacine Laabi | Paris Sud XI University (original) (raw)

Papers by Yacine Laabi

Science, Aug 11, 2000

... In addition, TACI has been found on activated T cells (18), indicating that BAFF and APRIL ma... more ... In addition, TACI has been found on activated T cells (18), indicating that BAFF and APRIL may regulate T cell activity. ... It is possible that abnormal regulation of TACI or BCMA signaling may also contribute to the development of tumors. ...

Investigative Ophthalmology & Visual Science, 2017

Regenerative medicine, 2015

In 2009 the International Stem Cell Banking Initiative (ISCBI) contributors and the Ethics Workin... more In 2009 the International Stem Cell Banking Initiative (ISCBI) contributors and the Ethics Working Party of the International Stem Cell Forum published a consensus on principles of best practice for the procurement, cell banking, testing and distribution of human embryonic stem cell (hESC) lines for research purposes [1], which was broadly also applicable to human induced pluripotent stem cell (hiPSC) lines. Here, we revisit this guidance to consider what the requirements would be for delivery of the early seed stocks of stem cell lines intended for clinical applications.

Stem Cells Translational Medicine, Mar 5, 2014

Hutchinson-Gilford progeria syndrome is a rare congenital disease characterized by premature agin... more Hutchinson-Gilford progeria syndrome is a rare congenital disease characterized by premature aging in children. Identification of the mutation and related molecular mechanisms has rapidly led to independent clinical trials testing different marketed drugs with a preclinically documented impact on those mechanisms. However, the extensive functional effects of those drugs remain essentially unexplored. We have undertaken a systematic comparative study of the three main treatments currently administered or proposed to progeria-affected children, namely, a farnesyltransferase inhibitor, the combination of an aminobisphosphonate and a statin (zoledronate and pravastatin), and the macrolide antibiotic rapamycin. This work was based on the assumption that mesodermal stem cells, which are derived from Hutchinson-Gilford progeria syndrome-induced pluripotent stem cells expressing major defects associated with the disease, may be instrumental to revealing such effects. Whereas all three treatments significantly improved misshapen cell nuclei typically associated with progeria, differences were observed in terms of functional improvement in prelamin A farnesylation, progerin expression, defective cell proliferation, premature osteogenic differentiation, and ATP production. Finally, we have evaluated the effect of the different drug combinations on this cellular model. This study revealed no additional benefit compared with single-drug treatments, whereas a cytostatic effect equivalent to that of a farnesyltransferase inhibitor alone was systematically observed. Altogether, these results reveal the complexity of the modes of action of different drugs, even when they have been selected on the basis of a similar mechanistic hypothesis, and underscore the use of induced pluripotent stem cell derivatives as a critical and powerful tool for standardized, comparative pharmacological studies.

In Vitro Cellular & Developmental Biology - Animal, 2010

Pre-implantation genetic diagnosis allows the characterisation of embryos that carry a gene respo... more Pre-implantation genetic diagnosis allows the characterisation of embryos that carry a gene responsible for a severe monogenic disease and to transfer to the mother's uterus only the unaffected one(s). The genetically affected embryos can be used to establish human embryonic stem cell (hESC) lines. We are currently establishing a cell bank of ESC lines carrying specific disease-causing mutant genes. These cell lines are available to the scientific community. For this purpose, we have designed a technique that requires only minimal manipulation of the embryos. At the blastocyst stage, we just removed the zona pellucida before seeding the embryo as a whole on a layer of feeder cells. This approach gave a good success rate (>20%), whatever the quality of the embryos, and allowed us to derive 11 new hESC lines, representing seven different pathologies. Full phenotypic validation of the cell lines according to ISCI guidelines confirmed their pluripotent nature, as they were positive for hESC markers and able to differentiate in vitro in all three germ layers derivatives. Nine out of 11 stem cell lines had normal karyotypes. Our results indicate that inner cell mass isolation is not mandatory for hESC derivation and that minimal manipulation of embryos can lead to high success rate.

Annals of the New York Academy of Sciences, 2006

Analysis of the critical cellular processes of self-generation, commitment, and maturation induct... more Analysis of the critical cellular processes of self-generation, commitment, and maturation induction ideally requires the use of clonal cultures using cells with a capacity to undergo all three processes. Preprogenitor cells from normal mouse marrow are proving useful cells for such studies. Cells of a newly established cloned leukemic cell line, the GB2, are providing a useful analogous leukemic system because GB2 cells form stratified subpopulations of clonogenic cells able to be clonally analyzed in vitro in which self-renewal is demonstrable, but in which near-normal maturation can be induced by a wide range of hematopoietic regulators.

The Journal of Immunology, 2001

Journal of Biological Chemistry, 2004

The Journal of Immunology, 2005

L'analyse moleculaire d'une translocation chromosomique t(4 ;16)(q26 ;p13) associee a un ... more L'analyse moleculaire d'une translocation chromosomique t(4 ;16)(q26 ;p13) associee a un lymphome t intestinal humain a permis d'isoler un adnc hybride resultant de la fusion du gene de l'interleukine 2 avec un nouveau gene localise sur le chromosome 16. Ce gene que nous avons nomme bcma (pour b-cell maturation) est exprime de maniere preferentielle dans la lignee lymphoide b et son taux de transcription semble etre lie au processus de differenciation des lymphocytes b. Nous avons d'une part caracterise l'organisation genomique du gene bcma. Nous avons d'autre part obtenu des anticorps diriges contre la proteine bcma recombinante. Ces anticorps reconnaissent un peptide de 21 kda uniquement dans les lignees lymphoides b matures. La proteine bcma est donc synthetisee in vivo. Nous avons demontre par fractionnement cellulaire, immunoprecipitation et immunofluorescence que la proteine bcma est integree dans la membrane d'un sous-compartiment de l'appa...

Proceedings of the National Academy of Sciences of the United States of America, 2003

Notch signaling is involved in numerous cell fate decisions in invertebrates and vertebrates. The... more Notch signaling is involved in numerous cell fate decisions in invertebrates and vertebrates. The Notch receptor is a type I transmembrane (TM) protein that undergoes two proteolytic steps after ligand binding, first by an ADAM (a distintegrin and metalloprotease) in the extracellular region, followed by gamma-secretase-mediated cleavage inside the TM domain. We demonstrate here that the murine ligand Delta1 (Dll1) undergoes the same sequence of cleavages, in an apparently signal-independent manner. Identification of the ADAM-mediated shedding site localized 10 aa N-terminal to the TM domain has enabled us to generate a noncleavable mutant. Kuzbanian/ADAM10 is involved in this processing event, but other proteases can probably substitute for it. We then show that Dll1 is part of a high-molecular-weight complex containing presenilin1 and undergoes further cleavage by a gamma-secretase-like activity, therefore releasing the intracellular domain that localizes in part to the nucleus. U...

Bioprocess and biosystems engineering, Jan 8, 2016

Consistent and robust manufacturing is essential for the translation of cell therapies, and the u... more Consistent and robust manufacturing is essential for the translation of cell therapies, and the utilisation automation throughout the manufacturing process may allow for improvements in quality control, scalability, reproducibility and economics of the process. The aim of this study was to measure and establish the comparability between alternative process steps for the culture of hiPSCs. Consequently, the effects of manual centrifugation and automated non-centrifugation process steps, performed using TAP Biosystems' CompacT SelecT automated cell culture platform, upon the culture of a human induced pluripotent stem cell (hiPSC) line (VAX001024c07) were compared. This study, has demonstrated that comparable morphologies and cell diameters were observed in hiPSCs cultured using either manual or automated process steps. However, non-centrifugation hiPSC populations exhibited greater cell yields, greater aggregate rates, increased pluripotency marker expression, and decreased diffe...

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International Immunology, 1995

BCMA is a human gene expressed preferentially in mature B lymphocytes as a 1.2 kb mRNA, which enc... more BCMA is a human gene expressed preferentially in mature B lymphocytes as a 1.2 kb mRNA, which encodes a 184 amino acid peptide (BCMAp). The study of BCMA mRNA expression, using human malignant B cell lines characteristic of different stages of B lymphocyte differentiation, demonstrated that the BCMA mRNA is absent in the pro-B lymphocyte stage. It is expressed faintly at the pre-B cell stage and its expression increases with B lymphocyte maturation. Polyclonal antibodies were used to show, by cellular fractionation and immunoprecipitation, that BCMAp is a non-glycosylated integral membrane protein. Furthermore, BCMAp inserts, in vitro, into canine microsomes, as a type I integral membrane protein. Cell surface labeling showed that BCMAp is not expressed in the plasma membrane of mature B lymphocytes. Immunofluorescence studies revealed that BCMAp lies in a cap-like structure near the nucleus, that was identified as the Golgi apparatus by co-localization of BCMAp with CTR433, a marker of the medial cisternae of the Golgi apparatus. Confocal scanning laser microscopy of U266 plasma cells labeled with markers of various Golgi apparatus subcompartments strongly suggests that BCMAp is located in the cis part of the Golgi apparatus. Thus, BCMAp is the first Golgi resident protein with a tissue specificity and whose expression is linked to the stage of differentiation of B lymphocytes. The location of BCMAp in the Golgi apparatus and its high expression in plasmocytes (secreting large amounts of Ig) suggest that BCMAp is implicated in the intracellular traffic of Ig.

Science, 2000

As if the TNF receptor and ligand superfamily was not big enough, two new receptors and their lig... more As if the TNF receptor and ligand superfamily was not big enough, two new receptors and their ligands have now been added to it. As Laâbi and Strasser explain in their Perspective, the receptors BCMA and TACI and their ligands BAFF/BLys and APRIL, respectively, are important for B lymphocyte survival, proliferation, and differentiation.