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NAD+-dependent Sirt6 is a key regulator involved in telomere shortening of in vitro-cultured preimplantation embryos

ABSTRACT: NAD+-dependent Sirt6 is a key regulator involved in telomere shortening of in vitro-cultured preimplantation embryos

PROVIDER: PRJNA1179958 | ENA |

REPOSITORIES: ENA

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NAD+-dependent Sirt6 is a key regulator involved in telomere shortening of in vitro-cultured preimplantation embryos

Project description:Telomere length is important for the maintaining the individual health of a species. However, recent studies have indicated that the telomere length of somatic cells can be drastically decreased in the offspring receiving in vitro fertilization (IVF) therapy, however, the underlying molecular mechanism remains unknown. Sirt6 is a NAD+-dependent epigenetic regulator that has recently been found to play an important role in maintaining telomere stability. Here, we report for the first time that NAD+ levels are significantly lower in blastocysts cultured in vitro than that in blastocysts developed in vivo, leading to impaired Sirt6 function, further triggering telomere shortening of the inner cell mass and possibly affecting newborn offspring. This phenotype could be effectively mitigated by supplementation with NMN, a precursor of NAD+, during in vitro culture.While it could not be achieved in Sirt6 conditional knockout embryos. Our results reveal the mechanism by which in vitro culture induces telomere shortening in preimplantation embryos, providing a potential target for improving in vitro culture conditions.

2025-07-07 | GSE280684 | GEO

NAD+-dependent Sirt6 is a key regulator involved in telomere shortening of in vitro-cultured preimplantation embryos [Bisulfite-Seq]

Project description:Telomere length (TL) is important for the maintaining the individual health of a species. However, recent studies have indicated that blastocyst culture may increase the risk of telomere shortening in the offspring of those undergoing in vitro fertilization (IVF) treatment, however, the underlying molecular mechanism remains unknown. Sirt6 is a NAD+-dependent epigenetic regulator that has recently been found to play an important role in maintaining telomere stability. Here, we report for the first time that NAD+ levels are significantly lower in blastocysts cultured in vitro than that in blastocysts developed in vivo, leading to impaired Sirt6 function, further triggering telomere shortening of the inner cell mass and possibly affecting newborn offspring. This phenotype could be effectively mitigated by supplementation with nicotinamide mononucleotide (NMN), a precursor of NAD+, during in vitro culture, while it could not be achieved in Sirt6 conditional knockout embryos. Furthermore, mtROS accumulation and epigenetic modifications may also play an important role in this process. Our results reveal the mechanism by which in vitro culture induces telomere shortening in preimplantation embryos, providing a potential target for improving in vitro culture conditions.

2025-07-07 | GSE299048 | GEO

NAD+-dependent Sirt6 is a key regulator involved in telomere shortening of in vitro-cultured preimplantation embryos [Bisulfite-Seq]

Project description:NAD+-dependent Sirt6 is a key regulator involved in telomere shortening of in vitro-cultured preimplantation embryos [Bisulfite-Seq]

| PRJNA1272457 | ENA

Telomere Shortening Impairs PGC Fate Decision

Project description:Telomere Shortening Impairs PGC Fate Decision

| PRJNA660792 | ENA

Gene expression changes by telomere shortening in human colonic organoids

Project description:Gene expression changes of UC-model organoids derive from human colon indcued by telomere enlongation was assessed by Madecassoside treatemt (telomerase activator). Gene expression changes of human colon organoids induced by telomere shortening was assessd by MST-312 treatment (telomerase inhibitor).

2021-06-24 | GSE175994 | GEO

Telomere Shortening Impairs PGC Fate Decision [ATAC-seq]

Project description:Telomere Shortening Impairs PGC Fate Decision [ATAC-seq]

| PRJNA660789 | ENA

Telomere Shortening Impairs PGC Fate Decision [RNA-seq]

Project description:Telomere Shortening Impairs PGC Fate Decision [RNA-seq]

| PRJNA660794 | ENA

Telomere shortening is associated with over-expression of subtelomeric genesin thyroid tumors.

Project description:To determine whether telomere shortening in thyroid tumors delineates gene expression of subtelomeric regions, we performed RNA sequencing in a set of tumors (n = 15) and compare gene expression profiles of subtelomeric and non-subtelomeric genes between short telomere tumors and normal telomere tumors. We defined as subtelomeric genes, those located within the 5 megabase windows (Mb) adjacent to the telomeres.

2022-08-24 | GSE193623 | GEO

Telomere Shortening Impairs PGC Fate Decision [RNA-seq]

Project description:We asked whether telomere shortening impairs differentiation of ESCs into germ cell lineage. Terc-/- ESCs were used to investigate the effects of short telomeres on germ cell specification by in vitro differentiation. Short telomeres greatly reduced induction of PGCLCs from ESCs. Mechanistically, short telomeres resulted in excessive chromatin accessibility, which in turn activated the genes regulated by chromatin. Notably, Fst overexpression reduced BMP-Smad signaling and thus induction of PGCLCs, meanwhile upregulation of MAPK signaling pathway increase somatic lineage differentiation in short telomeres sampels. Moreover, knockin of Terc gene by CRISPR/Cas9 in Terc-/- ESCs restored telomere length and normal gene expression profile, and rescued PGCLC induction, revealing important roles of telomeres in PGC fate decision.

2022-08-31 | GSE157303 | GEO

Telomere Shortening Impairs PGC Fate Decision [ATAC-seq]

2022-08-31 | GSE157301 | GEO