ArticleNature communications2024
Dynamic nucleolar phase separation influenced by non-canonical function of LIN28A instructs pluripotent stem cell fate decisions.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- Epigenetics in development, disease, and therapy: from mechanisms to clinical interventions.Science China. Life sciences · 2026Review
- Temporal dynamics of intragenic enhancer RNAs regulate Lin28a expression in response to external stimuli in embryonic stem cells.Nucleic acids research · 2026Article
- Granular component sub-phases direct ribosome biogenesis in the nucleolus.Molecular cell · 2026Article
- The RNA binding protein LIN28A mediates chromatin dynamics during neuronal differentiation.Cell death and differentiation · 2026Article
- Hyperactivation of mTORC1 blocks stem cell fate transitions through TFE3-NuRD association.EMBO reports · 2026Article
- Induced pluripotent stem cell reprogramming: methodological evolution and challenges in clinical translation.Frontiers in cell and developmental biology · 2026Review
- HypoxamiRs: the hidden architects of tissue adaptation in hypoxia.Cell death & disease · 2025Review
- Hypertranscription of rDNA Responsible for Nucleolar Remodelling is a Doorman for Acquiring Pluripotency.Cell proliferation · 2025Article
- Unveiling the dynamic drivers: phase separation's pivotal role in stem cell biology and therapeutic potential.Stem cell research & therapy · 2025Review
- Loss of intracellular ATP affects axoplasmic viscosity and pathological protein aggregation in mammalian neurons.Science advances · 2025Article
- Resveratrol inhibits Lin28A expression and induces its degradation via the proteasomal pathway in NCCIT cells.Oncology letters · 2024Article
- Membraneless organelles in health and disease: exploring the molecular basis, physiological roles and pathological implications.Signal transduction and targeted therapy · 2024Review
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
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.
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