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LIN28 Promotes Nucleolar/Ribosomal Functions and Phase Separation in Pluripotent Stem Cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE164420 | GEO | 2021/09/15

REPOSITORIES: GEO

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LIN28 Promotes Nucleolar/Ribosomal Functions and Phase Separation in Pluripotent Stem Cells

Project description:LIN28 Promotes Nucleolar/Ribosomal Functions and Phase Separation in Pluripotent Stem Cells

| PRJNA690578 | ENA

LIN28 Promotes Nucleolar Phase Separation to Regulate the ES/2C State Homeostasis in Pluripotent Stem Cells [Hi-C]

Project description:LIN28 is an RNA binding protein with important roles in early embryo development by interaction with let-7 microRNA precursors or mRNAs in cytoplasm. Here, we showed novel roles of LIN28 within the nucleolus in cultured pluripotent stem cells (PSCs). We found Lin28 deficiency led to activation of the 2-cell (2C)-like transcriptional program and repression of the ES cell program. Mechanistically, LIN28 maintains a peri-nucleolar heterochromatin-residing complex to repress 2C activator Dux via association with NCL and TRIM28. Meanwhile, it promotes liquid-liquid phase separation (LLPS) of nucleolar proteins FBL and NCL to support nucleolar function through its RNA binding domains and intrinsic disordered regions. These findings elucidate novel roles for nucleolar LIN28 in coordinately regulating the ES/2C state homeostasis, and shed light on RNA binding protein-mediated nucleolar phase separation mechanisms in PSCs and early embryo development.

2021-09-15 | GSE164414 | GEO

LIN28 Promotes Nucleolar Phase Separation to Regulate the ES/2C State Homeostasis in Pluripotent Stem Cells [CLIP-seq]

2021-09-15 | GSE164238 | GEO

LIN28 Promotes Nucleolar/Ribosomal Functions to Repress the 2C-like Transcriptional Program in Pluripotent Stem Cells [RNA-seq]

2021-09-15 | GSE164418 | GEO

LIN28 Promotes Nucleolar/Ribosomal Functions to Repress the 2C-like Transcriptional Program in Pluripotent Stem Cells [scRNA-seq]

2021-09-15 | GSE164296 | GEO

LIN28 Promotes Nucleolar/Ribosomal Functions to Repress the 2C-like Transcriptional Program in Pluripotent Stem Cells [ChIP-seq]

2021-09-15 | GSE164221 | GEO

LIN28 Promotes Nucleolar/Ribosomal Functions to Repress the 2C-like Transcriptional Program in Pluripotent Stem Cells [ATAC-seq]

2021-09-15 | GSE164130 | GEO

Dynamic nucleolar phase separation influenced by non-canonical function of LIN28A instructs pluripotent stem cell fate decisions.

Project description:LIN28A is important in somatic reprogramming and pluripotency regulation. Although previous studies addressed that LIN28A can repress let-7 microRNA maturation in the cytoplasm, few focused on its role within the nucleus. Here, we show that the nucleolus-localized LIN28A protein undergoes liquid-liquid phase separation (LLPS) in mouse embryonic stem cells (mESCs) and in vitro. The RNA binding domains (RBD) and intrinsically disordered regions (IDR) of LIN28A contribute to LIN28A and the other nucleolar proteins' phase-separated condensate establishment. S120A, S200A and R192G mutations in the IDR result in subcellular mislocalization of LIN28A and abnormal nucleolar phase separation. Moreover, we find that the naive-to-primed pluripotency state conversion and the reprogramming are associated with dynamic nucleolar remodeling, which depends on LIN28A's phase separation capacity, because the LIN28A IDR point mutations abolish its role in regulating nucleolus and in these cell fate decision processes, and an exogenous IDR rescues it. These findings shed light on the nucleolar function in pluripotent stem cell states and on a non-canonical RNA-independent role of LIN28A in phase separation and cell fate decisions.

| S-EPMC10858886 | biostudies-literature

LIN28 Promotes Nucleolar Phase Separation to Regulate the ES/2C State Homeostasis in Pluripotent Stem Cells [Hi-C]

Project description:LIN28 Promotes Nucleolar Phase Separation to Regulate the ES/2C State Homeostasis in Pluripotent Stem Cells [Hi-C]

| PRJNA690569 | ENA

LIN28 Promotes Nucleolar Phase Separation to Regulate the ES/2C State Homeostasis in Pluripotent Stem Cells [CLIP-seq]

Project description:LIN28 Promotes Nucleolar Phase Separation to Regulate the ES/2C State Homeostasis in Pluripotent Stem Cells [CLIP-seq]

| PRJNA689608 | ENA