Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Establishing competence for trophectoderm specification in mouse embryos before the first lineage bifurcation

ABSTRACT: How embryonic blastomeres transition from totipotency to differentiation remains a fundamental question in developmental biology. Here, we uncover the transcription factor CEBPa as an orchestrator of this process. CEBPa expression is first activated by NR5A2 at the 2-cell to 4-cell transition and in a second wave peaks in the trophectoderm of blastocysts. Loss of CEBPa disrupts timely blastocyst formation and impairs trophectoderm development, while its forced expression in embryonic stem cells drives differentiation into trophectoderm-like cells. Mechanistically, CEBPa sequentially activates key trophectoderm enhancers in a dose-dependent manner. At the 4-cell stage, some of these trophectoderm enhancers are already active while others are primed or still closed, placing blastomeres in a state of alert. These findings establish CEBPa as a molecular switch that equips 4-cell blastomeres with the competence for trophectoderm differentiation, defining the earliest steps in cell fate bifurcation and shedding new light on the mechanisms driving embryonic lineage specification.

ORGANISM(S): Mus musculus

PROVIDER: GSE284147 | GEO | 2025/10/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Establishing competence for trophectoderm specification in mouse embryos before the first lineage bifurcation [ChIP-seq]

Project description:How embryonic blastomeres transition from totipotency to differentiation remains a fundamental question in developmental biology. Here, we uncover the transcription factor CEBPa as an orchestrator of this process. CEBPa expression is first activated by NR5A2 at the 2-cell to 4-cell transition and in a second wave peaks in the trophectoderm of blastocysts. Loss of CEBPa disrupts timely blastocyst formation and impairs trophectoderm development, while its forced expression in embryonic stem cells drives differentiation into trophectoderm-like cells. Mechanistically, CEBPa sequentially activates key trophectoderm enhancers in a dose-dependent manner. At the 4-cell stage, some of these trophectoderm enhancers are already active while others are primed or still closed, placing blastomeres in a state of alert. These findings establish CEBPa as a molecular switch that equips 4-cell blastomeres with the competence for trophectoderm differentiation, defining the earliest steps in cell fate bifurcation and shedding new light on the mechanisms driving embryonic lineage specification.

2025-10-24 | GSE284146 | GEO

Establishing competence for trophectoderm specification in mouse embryos before the first lineage bifurcation [ATAC-seq]

2025-10-24 | GSE284145 | GEO

Establishing competence for trophectoderm specification in mouse embryos before the first lineage bifurcation [RNA-seq]

2025-10-24 | GSE284144 | GEO

Enhancer recruitment of transcription repressors RUNX1 and TLE3 by mis-expressed FOXC1 blocks differentiation in acute myeloid leukemia

Project description:Despite absent expression in normal hematopoiesis, the Forkhead factor FOXC1, a critical mesenchymal differentiation regulator, is highly expressed in ~30% of HOXAhigh AML to confer blocked monocyte/macrophage differentiation. Through integrated proteomics and bioinformatics, we discovered that FOXC1 and RUNX1 interact through Forkhead and Runt domains respectively and cooccupy primed and active enhancers distributed close to differentiation genes. FOXC1 stabilises association of RUNX1, HDAC1 and Groucho repressor TLE3 to limit enhancer activity: FOXC1 knockdown induced loss of repressor proteins, gain of CEBPA binding, enhancer acetylation and upregulation of nearby genes, including KLF2. Furthermore, it triggered genome-wide redistribution of RUNX1, TLE3 and HDAC1 from enhancers to promoters leading to repression of self-renewal genes including MYC and MYB. Our studies highlight RUNX1 and CEBPA transcription factor swapping as a feature of leukemia cell differentiation, and reveal that FOXC1 prevents this by stabilising enhancer binding of a RUNX1/HDAC1/TLE3 transcription repressor complex, to oncogenic effect.

2021-08-08 | PXD027740 | Pride

Cell fate inclination within 2-cell and 4-cell mouse embryos revealed by single-cell RNA sequencing

Project description:It remains an open question when and how the first cell fate decision is made in mammals. Using deep single-cell RNA-seq of matched sister blastomeres, we report highly reproducible interblastomere differences among ten 2-cell and five 4-cell mouse embryos. Inter-blastomere gene expression differences dominated between-embryo differences and noises, and were sufficient to cluster sister blastomeres into distinct groups. Dozens of protein-coding genes exhibited reproducible bimodal expression in sister blastomeres (0 vs. 1e3-1e6 of FPKM), which cannot be explained by random fluctuations. The protein expression of one of these bimodal genes, Gadd45a, exhibited clear inter-blastomeric contrasts. We traced some of the bimodal mRNA expressions to embryonic genome activation, and others to blastomere-specific RNA depletion. Inter-blastomere differences created co-expression gene networks that were much stronger and larger than those that can be possibly created by random noises. The highly correlated gene pairs at the 4-cell overlapped with those showing the same directions of differential expression between inner cell mass (ICM) and trophectoderm (TE). These data substantiate the hypothesis of inter-blastomere differences in 2- and 4-cell mouse embryos, and associate these differences with ICM/TE differences. 9 zygotes, 10 2-cell, and 5 4-cell mouse (C57BL/6) embryos were collected and multi-cell embryos were separated into blastomeres. 4 inner cell mass (ICM) and 3 trophectoderm (TE) samples are also extracted from mouse blastocysts. Transcriptome profiles for all samples are obtained via Smart-seq protocol.

2014-07-29 | E-GEOD-57249 | biostudies-arrayexpress

Label-free Quantification of Proteins in Single Embryonic Cells with Neural Fate in the Cleavage-Stage Frog (Xenopus laevis) Embryo using CE-ESI-HRMS

Project description:In this work, we integrate capillary electrophoresis electrospray ionization mass spectrometry, bottom-up proteomics, and single-cell microanalysis to enable the label-free quantification (LFQ) of proteins in single embryonic cells (D11 blastomeres) in the 16-cell frog (Xenopus laevis) embryo. Based on the LFQ data, we find translational differences between the blastomeres even within the same cell type.

2016-06-23 | PXD004174 | Pride

Remodeling the step-wise mouse placental development by using totipotent blastomere-like stem cells [scRNA-seq]

Project description:During development, totipotent blastomeres initiate the first cell fate decision to generate inner cell mass and trophectoderm. The trophectoderm forms the placenta mediating fetal-maternal communications, while placental deficiencies cause infertility and pregnancy disorders in humans. However, in vitro systems remodeling the step-wise placental development, particularly encompassing the pre-implantation phase, are still unavailable. Here, using mouse totipotent blastomere-like cells (TBLCs), we successfully realize inducing and long-term maintaining trophectoderm-like stem cells (TELSCs), and further generating placental trophoblast organoids. Interestingly, an intermediate morula trophectoderm-like cells (TELCs) were transiently induced from TBLCs, and quickly converted into TELSCs assembling blastocyst trophectoderm. In 3D culturing condition, TELSCs can form rosette-like structures at peri-implantation period, to eventually generate trophoblast organoids, in which trophoblast progenitors/giant cells, spongiotrophoblasts and syncytiotrophoblasts were all identified at the single-cell level. Transcriptomic and epigenomic analyses enable tracing the step-by-step transition from TBLCs to mature trophoblast lineages. Thus, this study provides a comprehensive differentiation system to understand and investigate placental development.

2025-01-01 | GSE251983 | GEO