Publications by authors named "Louis Faure"

6 Publications

  • Page 1 of 1

Single-cell transcriptomics of human embryos identifies multiple sympathoblast lineages with potential implications for neuroblastoma origin.

Nat Genet 2021 May 8;53(5):694-706. Epub 2021 Apr 8.

Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden.

Characterization of the progression of cellular states during human embryogenesis can provide insights into the origin of pediatric diseases. We examined the transcriptional states of neural crest- and mesoderm-derived lineages differentiating into adrenal glands, kidneys, endothelium and hematopoietic tissue between post-conception weeks 6 and 14 of human development. Our results reveal transitions connecting the intermediate mesoderm and progenitors of organ primordia, the hematopoietic system and endothelial subtypes. Unexpectedly, by using a combination of single-cell transcriptomics and lineage tracing, we found that intra-adrenal sympathoblasts at that stage are directly derived from nerve-associated Schwann cell precursors, similarly to local chromaffin cells, whereas the majority of extra-adrenal sympathoblasts arise from the migratory neural crest. In humans, this process persists during several weeks of development within the large intra-adrenal ganglia-like structures, which may also serve as reservoirs of originating cells in neuroblastoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-021-00818-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610777PMC
May 2021

Robust and Scalable Learning of Complex Intrinsic Dataset Geometry via ElPiGraph.

Entropy (Basel) 2020 Mar 4;22(3). Epub 2020 Mar 4.

Institut Curie, PSL Research University, 75005 Paris, France.

Multidimensional datapoint clouds representing large datasets are frequently characterized by non-trivial low-dimensional geometry and topology which can be recovered by unsupervised machine learning approaches, in particular, by principal graphs. Principal graphs approximate the multivariate data by a graph injected into the data space with some constraints imposed on the node mapping. Here we present ElPiGraph, a scalable and robust method for constructing principal graphs. ElPiGraph exploits and further develops the concept of elastic energy, the topological graph grammar approach, and a gradient descent-like optimization of the graph topology. The method is able to withstand high levels of noise and is capable of approximating data point clouds via principal graph ensembles. This strategy can be used to estimate the statistical significance of complex data features and to summarize them into a single consensus principal graph. ElPiGraph deals efficiently with large datasets in various fields such as biology, where it can be used for example with single-cell transcriptomic or epigenomic datasets to infer gene expression dynamics and recover differentiation landscapes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/e22030296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516753PMC
March 2020

Stem cell contributions to cementoblast differentiation in healthy periodontal ligament and periodontitis.

Stem Cells 2021 Jan 16;39(1):92-102. Epub 2020 Oct 16.

Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, UK.

Loss of tissue attachment as a consequence of bacterial infection and inflammation represents the main therapeutic target for the treatment of periodontitis. Cementoblasts, the cells that produce the mineralized tissue, cementum, that is responsible for connecting the soft periodontal tissue to the tooth, are a key cell type for maintaining/restoring tissue attachment following disease. Here, we identify two distinct stem cell populations that contribute to cementoblast differentiation at different times. During postnatal development, cementoblasts are formed from perivascular-derived cells expressing CD90 and perivascular-associated cells that express Axin2. During adult homeostasis, only Wnt-responsive Axin2+ cells form cementoblasts but following experimental induction of periodontal disease, CD90+ cells become the main source of cementoblasts. We thus show that different populations of resident stem cells are mobilized at different times and during disease to generate precursors for cementoblast differentiation and thus provide an insight into the targeting cells resident cells for novel therapeutic approaches. The differentiation of these stem cells into cementoblasts is however inhibited by bacterial products such as lipopolysaccharides, emphasizing that regeneration of periodontal ligament soft tissue and restoration of attachment will require a multipronged approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/stem.3288DOI Listing
January 2021

Single cell RNA sequencing identifies early diversity of sensory neurons forming via bi-potential intermediates.

Nat Commun 2020 08 21;11(1):4175. Epub 2020 Aug 21.

Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Somatic sensation is defined by the existence of a diversity of primary sensory neurons with unique biological features and response profiles to external and internal stimuli. However, there is no coherent picture about how this diversity of cell states is transcriptionally generated. Here, we use deep single cell analysis to resolve fate splits and molecular biasing processes during sensory neurogenesis in mice. Our results identify a complex series of successive and specific transcriptional changes in post-mitotic neurons that delineate hierarchical regulatory states leading to the generation of the main sensory neuron classes. In addition, our analysis identifies previously undetected early gene modules expressed long before fate determination although being clearly associated with defined sensory subtypes. Overall, the early diversity of sensory neurons is generated through successive bi-potential intermediates in which synchronization of relevant gene modules and concurrent repression of competing fate programs precede cell fate stabilization and final commitment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-17929-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442800PMC
August 2020

Prototypical pacemaker neurons interact with the resident microbiota.

Proc Natl Acad Sci U S A 2020 07 9;117(30):17854-17863. Epub 2020 Jul 9.

Department of Cell and Developmental Biology, Zoological Institute, University of Kiel, D-24118 Kiel, Germany;

Pacemaker neurons exert control over neuronal circuit function by their intrinsic ability to generate rhythmic bursts of action potential. Recent work has identified rhythmic gut contractions in human, mice, and hydra to be dependent on both neurons and the resident microbiota. However, little is known about the evolutionary origin of these neurons and their interaction with microbes. In this study, we identified and functionally characterized prototypical ANO/SCN/TRPM ion channel-expressing pacemaker cells in the basal metazoan by using a combination of single-cell transcriptomics, immunochemistry, and functional experiments. Unexpectedly, these prototypical pacemaker neurons express a rich set of immune-related genes mediating their interaction with the microbial environment. Furthermore, functional experiments gave a strong support to a model of the evolutionary emergence of pacemaker cells as neurons using components of innate immunity to interact with the microbial environment and ion channels to generate rhythmic contractions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1920469117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395494PMC
July 2020

Heterogeneity of spontaneous DNA replication errors in single isogenic cells.

Sci Adv 2018 06 20;4(6):eaat1608. Epub 2018 Jun 20.

INSERM U1001, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine Paris Descartes, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France.

Despite extensive knowledge of the molecular mechanisms that control mutagenesis, it is not known how spontaneous mutations are produced in cells with fully operative mutation-prevention systems. By using a mutation assay that allows visualization of DNA replication errors and stress response transcriptional reporters, we examined populations of isogenic cells growing under optimal conditions without exogenous stress. We found that spontaneous DNA replication errors in proliferating cells arose more frequently in subpopulations experiencing endogenous stresses, such as problems with proteostasis, genome maintenance, and reactive oxidative species production. The presence of these subpopulations of phenotypic mutators is not expected to affect the average mutation frequency or to reduce the mean population fitness in a stable environment. However, these subpopulations can contribute to overall population adaptability in fluctuating environments by serving as a reservoir of increased genetic variability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.aat1608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010332PMC
June 2018