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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 23, 2023 |
| Title |
Lineage regulators TFAP2C and NR5A2 function as bipotency activators in totipotent embryos |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Other
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| Summary |
During the first lineage segregation, a mammalian totipotent embryo differentiates into inner cell mass (ICM) and trophectoderm (TE). However, how transcription factors (TFs) regulate this earliest cell fate decision in vivo remains elusive, with their regulomes primarily inferred from cultured cells. Here, we investigated the TF regulomes during the first mouse lineage specification across 6 stages, spanning the pre-initiation, initiation, commitment, and maintenance phases. Unexpectedly, we found TFAP2C, a trophoblast regulator, bound and activated both early TE and ICM genes at the totipotent (2-8-cell) stages (“bipotency activation”). Tfap2c deficiency caused downregulation of early ICM genes, including Nanog, Nr5a2, Tdgf1, and early TE genes, including Tfeb and Itgb5 in 8-cell embryos. Transcription defects in both ICM and TE lineages were also found in blastocysts, accompanied by increased apoptosis and reduced cell numbers in ICMs. Upon trophoblast commitment, TFAP2C left early-ICM genes but acquired binding to late-TE genes in blastocysts where it co-bound with CDX2, and later to extra-embryonic ectoderm (ExE) genes where it cooperatively co-occupied with the former ICM regulator SOX2. Finally, “bipotency activation” in totipotent embryos also applied to a pluripotency regulator NR5A2 which similarly bound and activated both ICM and TE lineage genes at the 8-cell stage. These data reveal a unique transcription circuity of totipotency underpinned by highly adaptable lineage regulators.
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| Overall design |
By employing CUT&RUN, RNA-seq, and ATAC-seq, we systematically examined the genome wide TFAP2C, CDX2 and SOX2 chromatin binding and transcriptional functions in mouse early embryos.
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| Web link |
http://10.1038/s41594-023-01199-x
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| Contributor(s) |
Li L, Lai F, Xie W |
| Citation(s) |
38243114 |
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| Submission date |
Oct 20, 2022 |
| Last update date |
Apr 01, 2024 |
| Contact name |
Lijia Li |
| E-mail(s) |
lijiali1119@gmail.com
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| Organization name |
Tsinghua University
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| Department |
School of Life Science
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| Lab |
Wei Xie lab
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| Street address |
Haidian District
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| City |
Beijing |
| ZIP/Postal code |
100084 |
| Country |
China |
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| Platforms (3) |
| GPL18480 |
Illumina HiSeq 1500 (Mus musculus) |
| GPL21273 |
HiSeq X Ten (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (93)
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| Relations |
| BioProject |
PRJNA892723 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE216256_RAW.tar |
4.2 Gb |
(http)(custom) |
TAR (of BW, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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