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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Oct 05, 2021 |
| Title |
Genetic control of pluripotency epigenome informs differentiation bias in mouse embryonic stem cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Genetically diverse pluripotent stem cells (PSCs) display varied, heritable responses to differentiation cues in the culture environment. By harnessing these disparities through derivation of embryonic stem cells (ESCs) from the BXD mouse genetic reference panel, along with C57BL/6J (B6) and DBA/2J (D2) parental strains, we demonstrate genetically determined biases in lineage commitment and identify major regulators of the pluripotency epigenome. Upon transition to formative pluripotency using epiblast-like cells (EpiLCs), B6 quickly dissolves naïve networks adopting gene expression modules indicative of neuroectoderm lineages; whereas D2 retains aspects of naïve pluripotency with little bias in differentiation. Genetic mapping identifies 6 major trans-acting loci co-regulating chromatin accessibility and gene expression in ESCs and EpiLCs, indicating a common regulatory system impacting cell state transition. These loci distally modulate occupancy of pluripotency factors, including TRIM28, P300, and POU5F1, at hundreds of regulatory elements. One trans-acting locus on Chr 12 primarily impacts chromatin accessibility in ESCs; while in EpiLCs the same locus subsequently influences gene expression, suggesting early chromatin priming. Consequently, the distal gene targets of this locus are enriched for neurogenesis genes and were more highly expressed when cells carried B6 haplotypes at this Chr 12 locus, supporting genetic regulation of biases in cell fate. Spontaneous formation of embryoid bodies validated this with B6 showing a propensity towards neuroectoderm differentiation and D2 towards definitive endoderm, confirming the fundamental importance of genetic variation influencing cell fate decisions.
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| Overall design |
Bulk RNA-seq and ATAC-seq performed in ESCs and EpiLCs in biological replicates derived from C57BL/6J, DBA/2J and BXD mouse strains. ChIP-seq performed in biological replicate ESCs. Single cell RNA-seq performed in embryoid bodies.
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| Contributor(s) |
Baker C, Byers C |
| Citation(s) |
34931323 |
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| Submission date |
Jan 15, 2021 |
| Last update date |
Jan 04, 2022 |
| Contact name |
Christopher Baker |
| E-mail(s) |
christopher.baker@jax.org
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| Organization name |
The Jackson Laboratory
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| Street address |
600 Main St
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| City |
Bar Harbor |
| State/province |
ME |
| ZIP/Postal code |
04609 |
| Country |
USA |
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| Platforms (4)
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| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (180)
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| Relations |
| BioProject |
PRJNA692475 |
| SRA |
SRP301962 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE164935_POU5F1normcounts.tsv.gz |
1.0 Mb |
(ftp)(http) |
TSV |
| GSE164935_RAW.tar |
365.4 Mb |
(http)(custom) |
TAR (of CSV, MTX, TSV) |
| GSE164935_TRIM28normcounts.tsv.gz |
3.0 Mb |
(ftp)(http) |
TSV |
| GSE164935_epiatac_normcounts.tsv.gz |
27.4 Mb |
(ftp)(http) |
TSV |
| GSE164935_epilc_counts.norm.tsv.gz |
3.9 Mb |
(ftp)(http) |
TSV |
| GSE164935_esc_counts.norm.tsv.gz |
3.9 Mb |
(ftp)(http) |
TSV |
| GSE164935_escatac_normcounts.tsv.gz |
22.1 Mb |
(ftp)(http) |
TSV |
| GSE164935_escatacbxdpf1_normcounts.tsv.gz |
29.0 Mb |
(ftp)(http) |
TSV |
| GSE164935_escrnabxdpf1_normcounts.tsv.gz |
4.2 Mb |
(ftp)(http) |
TSV |
| GSE164935_p300normcounts.tsv.gz |
1.1 Mb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
| Processed data provided as supplementary file |
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