Deciphering the pluripotency continuum in vivo using the rabbit model

Autor: Bouchereau, Wilhelm, Afanassieff, Marielle, Moulin, Anaïs, Aksoy, Irène, Joly, Thierry, Savatier, Pierre, Beaujean, Nathalie
Přispěvatelé: Institut cellule souche et cerveau (U846 Inserm - UCBL1), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ISARA-Lyon
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: EMBL Conference: Transcription and Chromatin.
EMBL Conference: Transcription and Chromatin., Aug 2020, Heidelberg, Germany
Popis: International audience; Pluripotency describes the ability of a stem cell to give rise to all cell types in mature organisms. Two main types of pluripotent stem cells (PSCs) have been described: naïve and primed. In rodents, naïve-state pluripotency characterises mouse embryonic stem cells (mESCs) that have been derived from the pre-implantation epiblast. In primates (human and monkey) and lagomorphs (rabbits), ESCs only exist in the primed state of pluripotency. Primed-state pluripotency characterises the epiblast of developmentally more advanced embryos, closer to the commitment to differentiation. Contrary to naïve PSCs, PSCs in the primed state of pluripotency fail to make chimeras when introduced into host blastocysts. Several methods have been developed to reprogram human and monkey ESCs to naïve-like pluripotency using various cocktails of growth factors and small molecules. However, none of them works in rabbits, suggesting that the molecular network of naïve pluripotency differ between primates and lagomorphs. This study aimed to decipher the molecular signature of naïve pluripotency in the rabbit. Using single-cell 10x Chromium RNA-sequencing of rabbit embryos, we analysed the expression of genes regulating pluripotency, as well as genes involved in other processes that shape pluripotency (cell-cycle machinery, chromatin-related regulators, metabolism). From those data, we observed strong similarities between rabbits, primates, and rodents. However, we also observed differences in the expression of well-known marker of naïve pluripotency in mice, such as Zinc-Finger Protein 42 (ZFP42, also known as REX1) or Teratocarcinoma-Derived Growth Factor 1 (TDGF1, also known as CRIPTO). We also identified novel molecular markers useful to characterize naïve-state pluripotency in rabbits that could then be used to capture naïve-state pluripotency in rabbit PSCs.
Databáze: OpenAIRE