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Items: 3

1.

Deconstructing the dynamic transcriptional program of pluripotent stem cells.

(Submitter supplied) Pluripotent stem cells (PSCs) are capable of dynamic interconversion between distinct substates, but the regulatory circuits specifying these states and enabling transitions between them are not well understood. We set out to address this issue and map the landscape of gene expression variability in PSCs by single-cell expression profiling of PSCs under different chemical and genetic perturbations. We find that signaling factors and developmental regulators show highly variable expression in PSCs, with expression states for some variable genes heritable through multiple cell divisions. Expression variability and population heterogeneity can be influenced by perturbation of signaling pathways and chromatin regulators. Strikingly, either removal of mature miRNAs or pharmacologic blockage of external signaling pathways drives PSCs into a low-noise ground state characterized by a reconfigured pluripotency regulatory network, increased self-renewal efficiency, and a distinct chromatin state, an effect mediated by the action of opposing miRNA families on the c-myc / Lin28 / let-7 axis. These findings illuminate the causes of transcriptional heterogeneity in PSCs and their consequences for cellular decision-making.
Organism:
Mus musculus
Type:
Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing
Platforms:
GPL13112 GPL17021
441 Samples
Download data: CSV
Series
Accession:
GSE60749
ID:
200060749
2.

Illumina HiSeq 2000 (Mus musculus)

Platform
Accession:
GPL13112
ID:
100013112
3.

FBSLIF_Plate1_F12

Organism:
Mus musculus
Source name:
v6.5 mouse embryonic stem cells
Platform:
GPL13112
Series:
GSE60749
Download data
Sample
Accession:
GSM1486691
ID:
301486691
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