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| Status |
Public on Jun 14, 2023 |
| Title |
Single-Cell Gene Expression Analysis of First Trimester Placenta Samples Linked to Idiopathic Recurrent Pregnancy Loss |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The extravillous trophoblast (EVT) cell lineage is a key feature of placentation and critical for spiral artery remodeling and successful pregnancy. Our knowledge of transcriptional regulation driving EVT cell development is limited. Here, we mapped the transcriptome and epigenome landscape as well as chromatin interactions of human trophoblast stem (TS) cells and their transition into the differentiated EVT cell lineage. Chromatin accessibility in intergenic regions was more extensive in EVT cells than in TS cells in the stem state, which is consistent with increased enhancer-driven gene regulation. Using reference epigenome annotation, we noted that 18% of the chromatin landscape in EVT cells was uncharted. We linked regulatory regions to their cognate target genes and characterized the three-dimensional organization of the TS cell functional genome by high throughput chromosome conformation capture. Integration of chromatin accessibility, long-range chromatin interactions, transcriptomic, and transcription factor binding motif enrichment enabled identification of transcription factors and regulatory mechanisms associated with EVT cell lineage development. Subsequent analyses elucidated functional roles for TFAP2C, SNAI1 and EPAS1 in the regulation of EVT cell lineage development. EPAS1 was identified as an upstream regulator of key EVT cell transcription factors, including ASCL2 and SNAI1 and was together with its targets linked to diseases of pregnancy, including idiopathic recurrent pregnancy loss and low birth weight. Collectively, we have revealed activation of a dynamic regulatory network that provides a framework for understanding EVT cell specification in trophoblast cell lineage development and human placentation.
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| Overall design |
Villous tissue was isolated from the product of conception derived from patients with idopathic recurrent pregnancy loss (RPL) and analyzed using scRNAseq.
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| Contributor(s) |
Grundberg E, Wesley E, Cheung W, Koseva B, Marsh C |
| Citation(s) |
37563143 |
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| Submission date |
May 24, 2022 |
| Last update date |
Sep 20, 2023 |
| Contact name |
Boryana Koseva |
| E-mail(s) |
[email protected]
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| Organization name |
Children's Mercy Hospital
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| Department |
CMRI
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| Lab |
Grundberg Lab
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| Street address |
2420 Pershing Road
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| City |
Kansas City |
| State/province |
MO |
| ZIP/Postal code |
64108 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (4)
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| GSM6189369 |
Villous tissue 1, RPL, replicate 1, scRNAseq |
| GSM6189370 |
Villous tissue 2, RPL, replicate 1, scRNAseq |
| GSM6189371 |
Villous tissue 2, RPL, replicate 2, scRNAseq |
| GSM6189372 |
Villous tissue 3, RPL, replicate 1, scRNAseq |
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| Relations |
| BioProject |
PRJNA842012 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE204723_RAW.tar |
89.6 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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