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📰 Chance does things right!

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© Nicolas Allègre & Claire Chazaud

We all come from a single cell that first multiplies into identical cells and then differentiates from each other. After many stages of differentiation, cells as diverse as those of the skin (The skin is an organ composed of several layers of tissue. It plays, among other things, the …) orintestine (The intestine is the part of the digestive system that extends from the exit of the stomach to …) they are produced. In a study published in the journal Nature Communicationsscientists show that the chance (In ordinary language, the word possibility is used to express a lack of efficiency, otherwise …) it can decide the future identity of the cell.

During cell differentiation, identity changes are finely regulated by cascades of gene induction, usually through upstream internal changes (e.g. to enable (Activation can refer to 🙂 sequence of transcription factors) or external (molecular and / or mechanical exchanges with neighboring cells) to the cell. It is these upstream changes that determine the path of differentiation. However, in some cases, chance can decide the future identity of the cell.

Some days (The day or day is the interval between sunrise and sunset; it is the …) After fertilization (Fertilization, for organized living beings, is the phase of reproduction …) (3 days a mouse (The term topo is an ambiguous vulgar name that can designate, for French speakers, before …) and 6 in humans), the earliest cell differentiation ofembryo (An embryo (from ancient Greek ἔμϐρυον / embruon) is …)separating future cells from the placenta (The placenta is a unique organ that physically and biologically connects the embryo into …)is performed based on location internal (In France, this name designates a doctor, a pharmacist or a dental surgeon, at the …) or external of the cell, while the second differentiation into cells of the epiblast (which produces all the cells of the future individual) depends on a random mechanism. To become an epiblast, a cell has need (Needs are at the level of the interaction between the individual and the environment. It is …) several specific transcription factors that cooperate to initiate differentiation. However, in progenitor cells prior to differentiation, these transcription factors have expression levels that vary from cell to cell in an uncoordinated manner. Chance will ensure that in a few cells between about 25, these factors will be found together (In set theory, a set intuitively designates a collection …) at levels sufficient to trigger differentiation. Only these cells will be able to transform into an epiblast. Therefore, it is the random co-expression of these factors that would engage the cell in differentiation.

Scientists have identified one of these epiblast differentiation factors, NANOG, and have shown that without this factor there is no differentiation, cells get stuck at stage (A stadium (from the ancient Greek στ? Διον stadion, from the verb …) of the progenitor, the development of the embryo stops. However, NANOG alone does not appear to be able to induce differentiation, demonstrating that only cooperation with other factors, as yet unknown, allows this differentiation.

This random decision mechanism has mainly been studied in bacteria (Bacteria (bacteria) are prokaryotic single-celled living organisms, characterized …) or al drosophila (Drosophila (from the Greek drosos: dew and philos: he who loves) is an insect …) but it remains little explored in mammals although involved in hematopoiesis.

This discovery is intimately linked to Research (Scientific research primarily refers to all actions undertaken with a view to …) on ES embryonic stem cells (Nobel Prize 2007 for Evans, Capecchi and Smithies) and induced pluripotent cells iPS (Ips is a genus of insects in the order Coleoptera, subfamily …) (Nobel Prize 2012 for Yamanaka) because they are equivalent in vitro epiblastic cells. ES and iPS cells can potentially produce any a cell individual (The Wiktionary is a free and open source dictionary project similar to Wikipedia (both …) and are therefore important actors for the cell therapy (In the context of biotherapies, cell therapy aims to heal the cells …). Therefore, understanding how these epiblastic cells are produced leads to advances in the knowledge and use of ES and iPS stem cells.


At three days of development in mice (or 6 in humans), progenitor cells have a random composition of NANOG (N) and several factors (F1, F2, etc.). Only cells with the right combination of factors (N, F1, and F2; circled in green) will differentiate in the next phase into an epiblast. Right panel: Immunostaining of a mouse embryo at three days of development with epiblastic cells (red). Scale bar: 10 microns.
© Nicolas Allègre & Claire Chazaud

To know more:

NANOG initiates the fate of the epiblast by coordinating the expression of pluripotency genes
Nicolas Allègre, Sabine Chauveau, Cynthia Dennis, Yoan Renaud, Dimitri Meistermann, Lorena Valverde Estrella, Pierre Pouchin, Michel Cohen-Tannoudji, Laurent David and Claire Chazaud.
Nature Communications June 21, 2022. https://doi.org/10.1038/s41467-022-30858-8

Laboratory:
Institute Genetic (Genetics (from the Greek genno γεννώ = to give birth) is …), reproduction and development – GReD (Inserm / CNRS / Clermont Auvergne University) – 28 place Dunant. 63000 Clermont-Ferrand.

Contact:
Claire Chazaud – Inserm Research Director – claire.chazaud at uca (Uca is a genus of crabs of the Ocypodidae family. It includes a hundred species of …).Fr

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