Shugoshin 2A stabilizes heterochromatin complexes to suppress the 2-cell-like state in embryonic stem cells.

Panpan Shi, Kairang Jin, Guoxing Yin, Lin Liu

Abstract read

In one paragraph

Article in Stem cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Panpan ShiState Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300350, China; Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China.

Kairang JinState Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300350, China; Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China.

Guoxing YinState Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300350, China; Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China.

Lin LiuState Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300350, China; Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China; Tianjin Union Medical Center, Nankai University, Tianjin 300000, China; Haihe Laboratory of Cell Ecosystem, Tianjin 300020, China. Electronic address: liulin@nankai.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Two-cell (2C)-specific transcripts important for maternal zygotic transition, such as Zscan4 and endogenous retrovirus (MERVL), are sporadically expressed in approximately 1%-5% of an embryonic stem cell (ESC) population to maintain ESC and telomere homeostasis. However, the molecular mechanisms regulating the 2-cell-like state in ESCs are not fully understood. Here, we show that Sgo2a is an important suppressor of the 2-cell-like state and telomere length. Loss of Sgo2a reduces the enrichment of heterochromatic H3K9me3 on 2C genes, including Dux, Zscan4 gene clusters and downstream enhancers, resulting in activation of a 2-cell-like state. However, chromosome breakage was detected in Sgo2a-deficient ESCs. Mechanistically, SGO2A promotes the interaction between RIF1 and KAP1, regulates KAP1 ubiquitination, and maintains KAP1 stability at heterochromatin, repressing 2-cell genes. These results reveal a critical role for Sgo2a in suppressing the 2C-like state to maintain the homeostasis and genome stability of ESCs.

Indexed as

Cell Cycle ProteinsEmbryonic Stem CellsHeterochromatinMouse Embryonic Stem CellsAnimalsGenomic InstabilityHistonesMiceProtein BindingTelomere-Binding ProteinsTelomere HomeostasisTranscription FactorsTripartite Motif-Containing Protein 28UbiquitinationCell Cycle ProteinsHeterochromatinHistonesRif1 protein, mouseTelomere-Binding ProteinsTranscription FactorsTrim28 protein, mouseTripartite Motif-Containing Protein 28Zscan4c protein, mouse2-cell like stateDuxESCsH3K9me3KAP1RIF1SGO2AtelomereubiquitinationZscan4

Identifiers

PMID41759527

DOI10.1016/j.stemcr.2026.102824

PMCPMC12985361

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LicenceCC BY

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.