Cellule somatique | EPFL Graph Search

vignette|Caryotype couleur chromosomes L'ensemble des cellules somatiques, appelé soma, sont toutes les cellules formant le corps d'un organisme multicellulaire, c'est-à-dire toutes les cellules n'appartenant pas à la lignée germinale, telles que les gamètes, ou les cellules germinales. Ces dernières constituent le germen. Les cellules somatiques constituent généralement l'immense majorité des cellules constituant un individu. Théoriquement, ces cellules n'étant pas des cellules germinales (à l'origine des gamètes), elles ne transmettront jamais à leur descendance les mutations qu'elles ont pu subir. Cependant, chez les Spongiaires, des cellules somatiques non-différenciées forment la lignée germinale et, chez les Cnidaires, des cellules somatiques différenciées sont à l'origine de la lignée germinale. Mutations somatiques Comme toutes les cellules, une cellule somatique peut muter. Une mutation somatique, si elle est « viable » (si elle ne tue pas la cellule, l'organe

Analysis of centriole elimination during C. elegans oogenesis

Pierre Gönczy, Graham Knott, Tamara Mikeladze-Dvali, Petr Strnad, Lukas von Tobel

Centrosomes are the principal microtubule organizing centers (MTOCs) of animal cells and comprise a pair of centrioles surrounded by pericentriolar material (PCM). Centriole number must be carefully regulated, notably to ensure bipolar spindle formation and thus faithful chromosome segregation. In the germ line of most metazoan species, centrioles are maintained during spermatogenesis, but eliminated during oogenesis. Such differential behavior ensures that the appropriate number of centrioles is present in the newly fertilized zygote. Despite being a fundamental feature of sexual reproduction in metazoans, the mechanisms governing centriole elimination during oogenesis are poorly understood. Here, we investigate this question in C. elegans. Using antibodies directed against centriolar components and serial-section electron microscopy, we establish that centrioles are eliminated during the diplotene stage of the meiotic cell cycle. Moreover, we show that centriole elimination is delayed upon depletion of the helicase CGH-1. We also find that somatic cells make a minor contribution to this process, and demonstrate that the germ cell karyotype is important for timely centriole elimination. These findings set the stage for a mechanistic dissection of centriole elimination in a metazoan organism.

2012

Dynamics of the most common pathogenic mtDNA variant m.3243A > G demonstrate frequency-dependency in blood and positive selection in the germline

Konstantin Popadin

The A-to-G point mutation at position 3243 in the human mitochondrial genome (m.3243A > G) is the most common pathogenic mtDNA variant responsible for disease in humans. It is widely accepted that m.3243A > G levels decrease in blood with age, and an age correction representing similar to 2% annual decline is often applied to account for this change in mutation level. Here we report that recent data indicate that the dynamics of m.3243A > G are more complex and depend on the mutation level in blood in a bi-phasic way. Consequently, the traditional 2% correction, which is adequate 'on average', creates opposite predictive biases at high and low mutation levels. Unbiased age correction is needed to circumvent these drawbacks of the standard model. We propose to eliminate both biases by using an approach where age correction depends on mutation level in a biphasic way to account for the dynamics of m.3243A > G in blood. The utility of this approach was further tested in estimating germline selection of m.3243A > G. The biphasic approach permitted us to uncover patterns consistent with the possibility of positive selection for m.3243A > G. Germline selection of m.3243A > G shows an 'arching' profile by which selection is positive at intermediate mutant fractions and declines at high and low mutant fractions. We conclude that use of this biphasic approach will greatly improve the accuracy of modelling changes in mtDNA mutation frequencies in the germline and in somatic cells during aging.

OXFORD UNIV PRESS2022

A single-cell-based identification and characterisation of Aregs, an inhibitory subpopulation of adipose stem and precursor cells

Magda Zachara

Adipose tissue is an essential element in energy conservation mechanisms. Its unique plasticity is driven by the ability of adipocytes to accumulate and liberate lipids as a function of the energetic status of the organism. Given the recent rise in the global incidence of obesity, there is great interest in understanding the mechanisms behind disturbed energy balance. However, the heterogeneity of adipose tissue and of the somatic stem cells giving rise to mature adipocytes, makes it extremely challenging to characterise the cellular and molecular identity of fat depots. Single-cell RNA sequencing has recently enabled ground-breaking insights into the composition of complex cell populations. Our single cell-based dissection of adipogenic precursors revealed the existence of distinct cell sub-populations within the murine subcutaneous fat depot. We demonstrated that one of these populations, characterised by a high expression of F3 gene (encoding CD142), showed a completely non-adipogenic phenotype. Moreover, it revealed to be regulatory towards other adipose stem and precursor cells by supressing their ability to form adipocytes in a paracrine manner. These adipogenic regulatory cells, which we termed Aregs, proved to maintain their inhibitory properties in vivo and were shown phenotypically conserved in humans. We next established the robustness of Aregs as a novel cell sub-type in the context of various isolation strategies, the strength of the adipogenic cue and sex-based differences. Interestingly, we observed that Aregs isolated from the bourgeoning subcutaneous depots of new-born mice had high adipogenic propensity, suggesting that the appearance of classical phenotypical and functional properties of Aregs is development-dependent. In the light of the considerable implications of Aregs in adipose tissue composition and plasticity and, subsequently metabolic health, it is critical to understand the mechanism of their inhibitory nature. Integration of transcriptomic and proteomic datasets allowed us to identify a comprehensive set of highly specific candidates, which we validated in the context of Aregsâ identity and function. Our findings revealed a few potentially involved molecular actors. These include secreted factors CD142, GDF10 and MGP, which proved to be directly capable of inhibiting adipogenesis of Areg-depleted adipose stem and precursor cells, and transcription factors PKNOX2 and MEOX2, whose inactivation in Aregs compromised their ability to inhibit adipogenesis of co-cultured differentiating pre-adipocytes. Collectively, these molecules point out to a potential functional relationship of Aregs with vasculature as well as evoke a plausible association of Aregsâ phenotype to visceral-like non-adipogenic properties. We are now integrating these findings and completing them by investigating the transcriptional regulation and signalling pathways underlying the elusive mechanism of Aregsâ activity.

EPFL2020

A single-cell-based identification and characterisation of Aregs, an inhibitory subpopulation of adipose stem and precursor cells

Magda Zachara

EPFL2020