Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Lysosomal catabolic activity governs the exit of the murine totipotent 2-cell state by silencing early-embryonic retrotransposons [RNA-seq]

ABSTRACT: During the development in mouse early embryos, a subset of retrotransposons and genes are transiently expressed in the totipotent 2-cell embryos. These 2-cell-embryo-asscoiated (referred to as 2C) transcripts rapidly shut down their expression beyond the late 2-cell stage of embryos, and this timely shutdown governs the embryo to exit from the 2-cell stage. However, mechanisms regulating this wave of shutdown are not fully understood. In this study, we established a novel connection between lysosomal catabolic activity and 2C transcripts in regulating the exit of totipotent 2-cell state by using both in vitro 2-cell-like cells model and mouse embryos. Our results showed that the activation of lysosomal catabolism in mouse embryos governed the embryo to exit from the 2-cell state by suppressing the expression of 2C transcripts. Mechanistically, we found that lysosomal catabolic activity modulated 2C transcripts by inactivating transcriptional factors Tfe3/Tfeb and abolishing their transcriptional activation on 2C retrotransposons, MERVL/MT2-Mm. Collectively, our study elucidates the function of lysosomal activity in orchestrating transcriptomic landscape and early development in mouse embryos and reveals an unanticipated layer of transcriptional control on early-embryonic retrotransposons from lysosomal signaling.

ORGANISM(S): Mus musculus

PROVIDER: GSE247082 | GEO | 2024/08/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Lysosomal catabolic activity governs the exit of the murine totipotent 2-cell state by silencing early-embryonic retrotransposons [CUT&Tag]

Project description:During the development in mouse early embryos, a subset of retrotransposons and genes are transiently expressed in the totipotent 2-cell embryos. These 2-cell-embryo-asscoiated (referred to as 2C) transcripts rapidly shut down their expression beyond the late 2-cell stage of embryos, and this timely shutdown governs the embryo to exit from the 2-cell stage. However, mechanisms regulating this wave of shutdown are not fully understood. In this study, we established a novel connection between lysosomal catabolic activity and 2C transcripts in regulating the exit of totipotent 2-cell state by using both in vitro 2-cell-like cells model and mouse embryos. Our results showed that the activation of lysosomal catabolism in mouse embryos governed the embryo to exit from the 2-cell state by suppressing the expression of 2C transcripts. Mechanistically, we found that lysosomal catabolic activity modulated 2C transcripts by inactivating transcriptional factors Tfe3/Tfeb and abolishing their transcriptional activation on 2C retrotransposons, MERVL/MT2-Mm. Collectively, our study elucidates the function of lysosomal activity in orchestrating transcriptomic landscape and early development in mouse embryos and reveals an unanticipated layer of transcriptional control on early-embryonic retrotransposons from lysosomal signaling.

2024-08-25 | GSE247081 | GEO

The homeobox transcription factor DUXBL controls exit from totipotency

Project description:In mice, exit from the totipotent 2-cell (2C) embryo stage requires silencing of the 2C-associated transcriptional program. However, the molecular mechanisms involved in this process remain poorly understood. Here, we demonstrate that the 2C-specific transcription factor DUX mediates an essential negative feedback loop by inducing the expression of DUXBL to promote this silencing.We show that DUXBL gains accessibility to DUX-bound regions specifically upon DUX expression.Furthermore, we determine that DUXBL interacts with TRIM24 and TRIM33, members of the tripartite motif superfamily involved in gene silencing and co-localizes with them in nuclear foci upon DUX expression. Importantly, DUXBL overexpression impairs 2C-associated transcription, whereas Duxbl inactivation in ESC increases DUX-dependent induction of the 2C-transcriptional program. Consequently, DUXBL deficiency in embryos results in sustained expression of 2C-associated transcripts, leading to early developmental arrest.Our study identifies DUXBL as an essential regulator of totipotency exit enabling the first divergence of cell fates.

2023-12-07 | GSE234053 | GEO

Global analysis of expression upon RNA Pol I inhibition (iPol I) in ESCs

Project description:Immediately following fertilisation, the genomes of mammalian embryos undergo extensive reprogramming to generate a totipotent zygote with the capacity to form the entire developing organism and associated extraembryonic tissues. The embryo must also switch from dependence on maternal transcripts to transcribing from its own genome, and is accompanied in mice by rapid and transient upregulation of MERVL transposons and MERVL-driven genes at the 2-cell stage. The mechanisms and requirement for MERVL and 2-cell (2C) gene upregulation are poorly understood. Moreover, this program must be rapidly shut off upon 2C exit and developmental progression. Here, we report that robust ribosomal RNA synthesis and nucleolar integrity are essential for exit from the 2C state. 2-cell embryos and 2C-like cells show immature nucleoli with altered structure and reduced function, and we reveal that nucleolar disruption induces conversion to the 2C-like state in ESCs. Mechanistically, the 2C/MERVL activator Dux is held in perinucleolar chromatin in ESCs and released into the nucleoplasm upon nucleolar disruption or direct inhibition of nucleolar phase separation, leading to its rapid upregulation. In embryos, nucleolar disruption prevents proper Dux silencing and leads to 2-4 cell arrest. Our findings reveal an intriguing link between rRNA synthesis, nucleolar maturation and gene repression during early development.

2022-03-14 | GSE185424 | GEO

Lysosomal catabolic activity governs the exit of the murine totipotent 2-cell state by silencing early-embryonic retrotransposons

Project description:Lysosomal catabolic activity governs the exit of the murine totipotent 2-cell state by silencing early-embryonic retrotransposons

| PRJNA1036191 | ENA

Lysosomal catabolic activity governs the exit of the murine totipotent 2-cell state by silencing early-embryonic retrotransposons [CUT&Tag]

Project description:Lysosomal catabolic activity governs the exit of the murine totipotent 2-cell state by silencing early-embryonic retrotransposons [CUT&Tag]

| PRJNA1036201 | ENA

Lysosomal catabolic activity governs the exit of the murine totipotent 2-cell state by silencing early-embryonic retrotransposons [RNA-seq]

Project description:Lysosomal catabolic activity governs the exit of the murine totipotent 2-cell state by silencing early-embryonic retrotransposons [RNA-seq]

| PRJNA1036202 | ENA

RNA-seq of control siRNA, p150 siRNA and p60 siRNA transfected mES cells

Project description:Totipotent cells that resemble 2-cell stage embryos (2C-like cells) can arise with a very low frequency in ES cell cultures. Here we show that totipotent-like cells can be induced in vitro through the down-regulation of the chromatin assembly activity of CAF-1. Endogenous retroviruses and 2-cell stage specific genes are among the highest upregulated genes upon CAF-1 knockdown and the emerging totipotent-like cells exhibit the molecular characteristics of endogenous 2C-like cells and 2-cell embryos. CAF-1 depletion leads to increased accessibility at MERVL elements and to the up-regulation of neighbouring genes, thereby generating a transcriptional profile similar to that of 2-cell stage embryos.

2015-08-02 | E-MTAB-2684 | biostudies-arrayexpress

The homeobox transcription factor DUXBL controls exit from the totipotent 2C state [RNA-seq]

Project description:Upon exit from the totipotent 2-cell (2C) embryo stage, the 2C-associated transcriptional program needs to be efficiently silenced. However, the molecular mechanisms involved in this process remain mostly unknown. Here, we determined that the 2C-specific transcription factor DUX directly induced the expression of DUXBL to promote this silencing. CUT&RUN analysis revealed that DUXBL gained accessibility to DUX-bound regions in DUX-induced ESC while it was unable to bind those regions in uninduced cells. Importantly, DUX expression in Duxbl-knockout ESC caused increased induction of the 2C-transcriptional program, whereas DUXBL overexpression impaired 2C-associated transcription. Mechanistically, we determined that DUXBL interacted with TRIM24 and TRIM33, two members of the tripartite motif superfamily involved in gene silencing, and co-localized with them in nuclear condensates upon DUX expression. Importantly, DUXBL downregulation in mouse zygotes led to a penetrant 2C-stage arrest. Our data revealed an unexpected role for DUXBL in controlling the exit from totipotency.

2023-12-06 | GSE210891 | GEO

The homeobox transcription factor DUXBL controls exit from the totipotent 2C state [Cut&Run]

2023-12-06 | GSE210890 | GEO

Chemical-induced chromatin remodeling reprograms mouse ESCs to totipotent-like stem cells [ChIP-seq]

Project description:Totipotent cells have more robust developmental potency than any other cell types, giving rise to both embryonic and extraembryonic tissues. Stable totipotent cultures and deciphering the principles of totipotency regulation would be invaluable to understand cell plasticity and lineage segregation in early development. Our approach of remodeling the pericentromeric heterochromatin and re-establishing the totipotency-specific broad H3K4me3 domains promotes the pluri-to-totipotency transition. Our protocol establishes a closer match of mouse 2-cell (2C) embryos than any other 2C-like cells. These totipotent-like stem cells (TLSCs) are stable in culture and possess unique molecular features of the mouse 2C embryo. Functionally, TLSCs are competent for germline transmission and give rise to both embryonic and extraembryonic lineages at high frequency. Therefore, TLSCs represent a highly valuable cell type for studies of totipotency and embryology.

2022-02-11 | GSE166208 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data