Wnt/β-Catenin Activation by iCRT3 Enhanced the Pluripotency of Bovine Expanded Pluripotent Stem Cells.

Dongsong Liu, Burong Qu, Jing Wang, Xu Han, Mengrui Su, Xihe Li, Yao Li, Xueling Li

Abstract read

In one paragraph

Article in Animals : an open access journal from MDPI, 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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0cells of the map it votes in

0citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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0 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Dongsong LiuThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, China.

Burong QuThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, China.

Jing WangThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, China.

Xu HanThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, China.

Mengrui SuThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, China.

Xihe LiThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, China.ORCID 0000-0002-7001-7997

Yao LiThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, China.

Xueling LiThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, China.ORCID 0000-0001-7995-0452

Funding

National Natural Science Foundation of China 32160172Natural Science Foundation of Inner Mongolia Autonomous Region 2024QN03010Science and Technology Major Project of the Inner Mongolia Autonomous Region of China to the State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock 2023KYPT0010 & 2021ZD0048the development plan for young scientific and technological talents in colleges and universities of Inner Mongolia Autonomous Region of China NMGIRT2204

6 · The paper itself

Abstract

The Wnt/β-catenin signaling pathway is involved in regulating the pluripotency of mammalian stem cells. Fine-tuning of Wnt/β-catenin modulates the transition of naïve, formative or primed states with distinct lineage bias. However, its specific function in large domestic animals such as bovines remains unclear. Here we systematically investigated the role of Wnt/β-catenin signaling and its key effector TCF1 in bovine expanded pluripotent stem cells (bEPSCs) using a combination of small molecules (CHIR99021, XAV939, IWR-1, iCRT3). The results showed that prolonged Wnt/β-catenin activation with CHIR99021 induced morphological changes and downregulated the expression of core pluripotency genes POU5F1 (OCT4) and SOX2 in bEPSCs, while the existence of Wnt/β-catenin inhibitors XAV939 and IWR-1 upregulated these two genes. Knockdown of TCF1, a major nuclear effector of CTNNB1 (β-catenin), reduced the expression of pluripotency genes (POU5F1, SOX2) and key Wnt/β-catenin components (TCF3, LEF1 and CTNNB1). Combined treatment with CHIR99021 and the canonical β-catenin/TCF inhibitor iCRT3 resulted in the overactivation of Wnt/β-catenin signaling, and promoted the expression of core pluripotency genes, revealing extensive rewiring of the Wnt/β-catenin pathway in bovines. Consistent with these findings, global transcriptomics revealed that CHIR99021 combined with iCRT3 enhanced the expression of key pluripotency-related genes and further activated Wnt/β-catenin signaling target genes while simultaneously suppressing mitogenic pathways such as PI3K-Akt and MAPK signaling. Transcriptome profiling also demonstrated that this combination drives bEPSCs toward a hybrid naïve/formative pluripotency state. Together, these results demonstrate that Wnt/β-catenin signaling homeostasis is critical for bovine pluripotency regulation, which provides a foundation for refining livestock stem cell culture conditions and understanding the evolution of pluripotency networks.

Indexed as

bEPSCsiCRT3pluripotency genesTCF1Wnt/β-catenin signaling pathway

Identifiers

PMID41750997

DOI10.3390/ani16040535

PMCPMC12937258

What Socratic holds

Textmetadata

LicenceCC BY

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Registered trials

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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 Socratic graph.