The RNA Helicase DDX6 Controls Cellular Plasticity by Modulating P-Body Homeostasis.
Bruno Di Stefano, En-Ching Luo, Chuck Haggerty, Stefan Aigner, Jocelyn Charlton, Justin Brumbaugh, Fei Ji, Inés Rabano Jiménez, Katie J Clowers, Aaron J Huebner, Kendell Clement, Inna Lipchina, Marit A C de Kort, Anthony Anselmo, John Pulice, Mattia F M Gerli, Hongcang Gu, Steven P Gygi, Ruslan I Sadreyev, Alexander Meissner, Gene W Yeo, Konrad Hochedlinger
Cell stem cell · 2019 · Vol. 25 (5) · pp. 622-638.e13
Abstract
Post-transcriptional mechanisms have the potential to influence complex changes in gene expression, yet their role in cell fate transitions remains largely unexplored. Here, we show that suppression of the RNA helicase DDX6 endows human and mouse primed embryonic stem cells (ESCs) with a differentiation-resistant, "hyper-pluripotent" state, which readily reprograms to a naive state resembling the preimplantation embryo. We further demonstrate that DDX6 plays a key role in adult progenitors where it controls the balance between self-renewal and differentiation in a context-dependent manner. Mechanistically, DDX6 mediates the translational suppression of target mRNAs in P-bodies. Upon loss of DDX6 activity, P-bodies dissolve and release mRNAs encoding fate-instructive transcription and chromatin factors that re-enter the ribosome pool. Increased translation of these targets impacts cell fate by rewiring the enhancer, heterochromatin, and DNA methylation landscapes of undifferentiated cell types. Collectively, our data establish a link between P-body homeostasis, chromatin organization, and stem cell potency.
Linked datasets 10
The RNA helicase DDX6 regulates self-renewal and differentiation of human and mouse stem cells [RNA-Seq]
Homo sapiens
10 data files
| File | Type | Size |
|---|---|---|
| Myoblast.shCTRL_1.R1.fastq.gz | RNA-Seq | 1.3 GB |
| Myoblast.shCTRL_2.R1.fastq.gz | RNA-Seq | 1.7 GB |
| Myoblast.shDDX6_1.R1.fastq.gz | RNA-Seq | 1.5 GB |
| Myoblast.shDDX6_1.R1.fastq.gz | RNA-Seq | 1.5 GB |
| Myoblast.shDDX6_2.R1.fastq.gz | RNA-Seq | 1.6 GB |
| Myoblast.shDDX6_2.R2.fastq.gz | RNA-Seq | 1.6 GB |
| NPC.shCTRL_1.R1.fastq.gz | RNA-Seq | 1.7 GB |
| NPC.shCTRL_2.R1.fastq.gz | RNA-Seq | 996.9 MB |
| NPC.shDDX6_1.R1.fastq.gz | RNA-Seq | 1.6 GB |
| NPC.shDDX6_2.R1.fastq.gz | RNA-Seq | 2.2 GB |
The RNA helicase DDX6 regulates self-renewal and differentiation of human and mouse stem cells [RNA-seq2]
Homo sapiens
10 data files
| File | Type | Size |
|---|---|---|
| CTRL-TESR-1_R1.fastq.gz | RNA-Seq | 1.2 GB |
| CTRL-TESR-2_R1.fastq.gz | RNA-Seq | 1.1 GB |
| CTRL-TGFBI-1_R1.fastq.gz | RNA-Seq | 1.1 GB |
| CTRL-TGFBI-2_R1.fastq.gz | RNA-Seq | 1.3 GB |
| DDXOE-TESR-1_R1.fastq.gz | RNA-Seq | 1.4 GB |
| DDXOE-TESR-2_R1.fastq.gz | RNA-Seq | 1.0 GB |
| DDXOE-TGFBI-1_R1.fastq.gz | RNA-Seq | 1.2 GB |
| DDXOE-TGFBI-1_R1.fastq.gz | RNA-Seq | 1.2 GB |
| DDXOE-TGFBI-2_R1.fastq.gz | RNA-Seq | 1.4 GB |
| DDXOE-TGFBI-2_R1.fastq.gz | RNA-Seq | 1.4 GB |
The RNA helicase DDX6 regulates self-renewal and differentiation of human and mouse stem cells [ChIP-Seq]
Homo sapiens
10 data files
| File | Type | Size |
|---|---|---|
| CTRL_H3K27ac_rep1.bam | ChIP-Seq | 162.8 MB |
| CTRL_H3K27ac_rep2.bam | ChIP-Seq | 177.2 MB |
| CTRL_H3K9me3_rep1.bam | ChIP-Seq | 92.0 MB |
| CTRL_H3K9me3_rep2.bam | ChIP-Seq | 257.7 MB |
| DDX6_H3K27ac_rep1.bam | ChIP-Seq | 136.4 MB |
| DDX6_H3K27ac_rep2.bam | ChIP-Seq | 223.0 MB |
| DDX6_H3K4me3_rep1.bam | ChIP-Seq | 113.2 MB |
| DDX6_H3K4me3_rep2.bam | ChIP-Seq | 150.6 MB |
| DDX6_H3K9me3_rep1.bam | ChIP-Seq | 87.4 MB |
| DDX6_H3K9me3_rep2.bam | ChIP-Seq | 244.5 MB |
The RNA helicase DDX6 regulates self-renewal and differentiation of human and mouse stem cells
Homo sapiens
The RNA helicase DDX6 regulation in human skeletal myoblasts [eCLIP-seq]
Homo sapiens
8 data files
| File | Type | Size |
|---|---|---|
| SRR8501416 | RIP-Seq | 422.7 MB |
| SRR8501416 | RIP-Seq | 422.7 MB |
| SRR8501417 | RIP-Seq | 532.8 MB |
| SRR8501417 | RIP-Seq | 532.8 MB |
| SRR8501418 | RIP-Seq | 727.0 MB |
| SRR8501418 | RIP-Seq | 727.0 MB |
| SRR8501419 | RIP-Seq | 700.6 MB |
| SRR8501419 | RIP-Seq | 700.6 MB |
The RNA helicase DDX6 regulates self-renewal and differentiation of human and mouse stem cells [RNA-seq]
Homo sapiens
10 data files
| File | Type | Size |
|---|---|---|
| GEN1C_sgCTRL_TGFBi_rep1.fastq.gz | RNA-Seq | 1.5 GB |
| GEN1C_sgCTRL_TGFBi_rep2.fastq.gz | RNA-Seq | 1.4 GB |
| GEN1C_sgDDX6_TGFBi_rep1.fastq.gz | RNA-Seq | 1.4 GB |
| GEN1C_sgDDX6_TGFBi_rep2.fastq.gz | RNA-Seq | 1.4 GB |
| WIBR3_Naive_rep1.fastq.gz | RNA-Seq | 895.0 MB |
| WIBR3_Naive_rep2.fastq.gz | RNA-Seq | 823.3 MB |
| WIBR3_shCTRL_TGFBi_rep1.fastq.gz | RNA-Seq | 1.7 GB |
| WIBR3_shCTRL_TGFBi_rep2.fastq.gz | RNA-Seq | 1.4 GB |
| WIBR3_shDDX6_TGFBi_rep1.fastq.gz | RNA-Seq | 1.6 GB |
| WIBR3_shDDX6_TGFBi_rep2.fastq.gz | RNA-Seq | 1.4 GB |
The RNA helicase DDX6 regulates self-renewal and differentiation of human and mouse stem cells [CLIP-Seq]
Homo sapiens
10 data files
| File | Type | Size |
|---|---|---|
| EY_INPUT_DCP1B_H1_S2_L006_R1_001.fastq.gz | RIP-Seq | 673.2 MB |
| EY_INPUT_FUS_H1_S1_L006_R1_001.fastq.gz | RIP-Seq | 477.5 MB |
| EY_INPUT_ILF2_H1_S3_L006_R1_001.fastq.gz | RIP-Seq | 618.7 MB |
| EY_IP_DCP1B_H1_S5_L006_R1_001.fastq.gz | RIP-Seq | 588.3 MB |
| EY_IP_FUS_H1_S4_L006_R1_001.fastq.gz | RIP-Seq | 567.4 MB |
| EY_IP_ILF2_H1_S6_L006_R1_001.fastq.gz | RIP-Seq | 455.5 MB |
| SA_DX6Ai_S97_L007_R1_001.fastq.gz | RIP-Seq | 2.1 GB |
| SA_DX6A_S98_L007_R1_001.fastq.gz | RIP-Seq | 1.6 GB |
| SA_DX6Bi_S99_L007_R1_001.fastq.gz | RIP-Seq | 1.7 GB |
| SA_DX6B_S100_L007_R1_001.fastq.gz | RIP-Seq | 900.5 MB |
The RNA helicase DDX6 regulates self-renewal and differentiation of human and mouse stem cells [ATAC-Seq]
Homo sapiens
10 data files
| File | Type | Size |
|---|---|---|
| iPSC.CTRL.1.R1.fastq.gz | ATAC-seq | 2.5 GB |
| iPSC.CTRL.2.R1.fastq.gz | ATAC-seq | 2.4 GB |
| iPSC.DDX6.1.R1.fastq.gz | ATAC-seq | 2.2 GB |
| iPSC.DDX6.2.R1.fastq.gz | ATAC-seq | 2.3 GB |
| Myoblast.CTRL.1.R1.fastq.gz | ATAC-seq | 2.4 GB |
| Myoblast.CTRL.2.R1.fastq.gz | ATAC-seq | 2.0 GB |
| Myoblast.DDX6.1.R1.fastq.gz | ATAC-seq | 2.0 GB |
| Myoblast.DDX6.1.R1.fastq.gz | ATAC-seq | 2.0 GB |
| Myoblast.DDX6.2.R1.fastq.gz | ATAC-seq | 2.3 GB |
| Myoblast.DDX6.2.R2.fastq.gz | ATAC-seq | 2.3 GB |
The RNA helicase DDX6 regulates self-renewal and differentiation of human and mouse stem cells [RRBS]
Homo sapiens
10 data files
| File | Type | Size |
|---|---|---|
| ESC_sgCTRL.1.R1.fq.gz | Bisulfite-Seq | 661.0 MB |
| ESC_sgCTRL.2.R1.fq.gz | Bisulfite-Seq | 631.9 MB |
| ESC_sgCTRL.3.R1.fq.gz | Bisulfite-Seq | 629.7 MB |
| ESC_sgCTRL.4.R1.fq.gz | Bisulfite-Seq | 614.6 MB |
| ESC_sgDDX6.1.R1.fq.gz | Bisulfite-Seq | 461.4 MB |
| ESC_sgDDX6.1.R1.fq.gz | Bisulfite-Seq | 461.4 MB |
| ESC_sgDDX6.2.R1.fq.gz | Bisulfite-Seq | 440.9 MB |
| ESC_sgDDX6.2.R1.fq.gz | Bisulfite-Seq | 440.9 MB |
| ESC_sgDDX6.3.R1.fq.gz | Bisulfite-Seq | 447.1 MB |
| ESC_sgDDX6.4.R1.fq.gz | Bisulfite-Seq | 436.4 MB |
The RNA helicase DDX6 regulates self-renewal and differentiation of human and mouse stem cells [polysome RNA-seq]
Homo sapiens
10 data files
| File | Type | Size |
|---|---|---|
| SRR8501406 | RNA-Seq | 602.5 MB |
| SRR8501407 | RNA-Seq | 590.9 MB |
| SRR8501408 | RNA-Seq | 429.8 MB |
| SRR8501409 | RNA-Seq | 606.9 MB |
| SRR8501410 | RNA-Seq | 359.6 MB |
| SRR8501411 | RNA-Seq | 716.7 MB |
| SRR8501412 | RNA-Seq | 621.7 MB |
| SRR8501413 | RNA-Seq | 654.2 MB |
| SRR8501414 | RNA-Seq | 754.0 MB |
| SRR8501415 | RNA-Seq | 529.2 MB |
Funding 5 grants
| Grant | Funder |
|---|---|
| P30 DK040561 | NIDDK NIH HHS (United States) |
| P01 GM099117 | NIGMS NIH HHS (United States) |
| P01 GM099134 | NIGMS NIH HHS (United States) |
| R01 GM067945 | NIGMS NIH HHS (United States) |
| R01 HD058013 | NICHD NIH HHS (United States) |