Biology subjects

Cohen-Tannoudji, M.

Publications and source records attributed to Cohen-Tannoudji, M..

3 recordsLinked to original sources

bioRxiv2018

Development of a robust automated tool for the annotation of embryo morphokinetic parameters

Study QuestionIs it possible to automatically annotate human embryo development in time-lapse devices, with results comparable to manual annotation?\n\nSummary AnswerWe developed an automated tool for the annotation of embryo morphokinetic parameters having a high concordance with expert manual annotation in a large scale-study.\n\nWhat is Known AlreadyMorphokinetic parameters obtained with time-lapse devices are increasingly used for human embryo quality assessment. However, their annotation is timeconsuming and can be operator-dependent, highlighting the need of developing automated approaches.\n\nStudy Design, Size, DurationThis monocentric pilot study was conducted using 701 blastocysts originating from 584 couples undergoing IVF with embryo culture in a time-lapse device and on 4 mouse embryos.\n\nParticipants/Materials, Setting, MethodsAn automated annotation tool was developed based on grey level coefficient of variation and detection of the thickness of the zona pellucida. The timings of cellular events obtained with the automated tool were compared with those obtained manually by 2 expert embryologists. The same procedure was applied on 4 mouse preimplantation embryos obtained with a different device in a different setting.\n\nMain Results and the Role of ChanceAlthough some differences were found when embryos were considered individually, we found an overall excellent concordance between automated and manual annotation of human embryo morphokinetics from fertilization to expanded blastocyst stage (r2=0.94). Moreover, the automated annotation tool gave promising results across species (human, mice).\n\nLimitations, Reasons for CautionThese results should undergo multi-centric external evaluation in order to test the overall performance of the annotation tool.\n\nWider Implications of the FindingsOur system performs significantly better than the ones reported in the literature and on a bigger cohort, paving the way for high-throughput analysis of multicentric morphokinetic databases, providing new insights into the clinical value of morphokinetics as predictor of embryo quality and implantation.\n\nStudy Funding/Competing Interest(s)This study was partly funded by Finox Forward Grant 2016.\n\nTrial Registration NumberNA

developmental biology↗

bioRxiv2018

Transcription factor activity and nucleosome organisation in mitosis

Mitotic bookmarking transcription factors (BFs) maintain the capacity to bind to their targets during mitosis, despite major rearrangements of the chromatin. While they were thought to propagate gene regulatory information through mitosis by statically occupying their DNA targets, it has recently become clear that BFs are highly dynamic in mitotic cells. This represents both a technical and a conceptual challenge to study and understand the function of BFs: first, formaldehyde has been suggested to be unable to efficiently capture these transient interactions, leading to profound contradictions in the literature; second, if BFs are not permanently bound to their targets during mitosis, it becomes unclear how they convey regulatory information to daughter cells. Here, comparing formaldehyde to alternative fixatives we clarify the nature of the chromosomal association of previously proposed BFs in embryonic stem cells: while Esrrb can be considered as a canonical BF that binds at selected regulatory regions in mitosis, Sox2 and Oct4 establish DNA sequence independent interactions with the mitotic chromosomes, either throughout the chromosomal arms (Sox2) or at pericentromeric regions (Oct4). Moreover, we show that ordered nucleosomal arrays are retained during mitosis at Esrrb book-marked sites, whereas regions losing transcription factor binding display a profound loss of order. By maintaining nucleosome positioning during mitosis, Esrrb might ensure the rapid post-mitotic re-establishment of functional regulatory complexes at selected enhancers and promoters. Our results provide a mechanistic framework that reconciles dynamic mitotic binding with the transmission of gene regulatory information across cell division.

genomics↗

bioRxiv2017

ICM conversion to epiblast by FGF/ERK inhibition is limited in time and requires transcription and protein degradation

Abbreviations used in this study\n\nAbstractInner cell Mass (ICM) specification into epiblast (Epi) and primitive endoderm (PrE) is an asynchronous and progressive process taking place between E3.0 to E3.75 under the control of the FGF/ERK signaling pathway. Here, we have analyzed in details the kinetics of specification and found that ICM cell responsiveness to the up and down regulation of FGF signaling activity are temporally distinct. We also showed that PrE progenitors are generated later than Epi progenitors. We further demonstrated that, during this late phase of specification, a 4 hours period of FGF/ERK inhibition prior E3.75 is sufficient to convert ICM cells into Epi. Finally, we showed that ICM conversion into Epi in response to inhibition during this short time window requires both transcription and proteasome degradation. Collectively, our data give new insights into the timing and mechanisms involved in the process of ICM specification.

developmental biology↗