Khdrbs1 drives redifferentiation of bipotential progenitor cell by inhibiting p53 in zebrafish biliary-mediated liver regeneration.

IF 3.7 2区生物学 Q1 DEVELOPMENTAL BIOLOGY

Development Pub Date : 2025-02-13 DOI:10.1242/dev.204266

Kai Gang, Qi Chen, Junhui Sun, Tingwei Zhang, Pengcheng Cai, Rui Ni, Jianlong Ma

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引用次数: 0

Abstract

After severe liver injury, biliary epithelial cells (BECs) undergo dedifferentiation into bipotential progenitor cells (BPPCs), which subsequently redifferentiate into nascent hepatocytes and BECs to accomplish liver regeneration. However, the critical factors governing the redifferentiation process of BPPCs remain largely unknown. Here, using a zebrafish model of severe liver injury, we observed specific expression of khdrbs1a and khdrbs1b (collectively known as khdrbs1) in BPPCs through single-cell RNA analyses and fluorescence in situ hybridization. Subsequently, to eliminate the genetic compensation, we generated a CRISPR/dead Cas9-mediated system for interfering khdrbs1 in BECs, which caused the defective liver regeneration and impaired redifferentiation of BPPCs. Furthermore, the khdrbs1-/- mutant displayed impaired proliferation and redifferentiation of BPPCs during liver regeneration. Mechanistically, p53 signaling was activated in response to the loss of khdrbs1, and tp53 mutation partially rescued the defective liver regeneration of the khdrbs1-/- mutant. In summary, we elucidate that Khdrbs1 promotes the redifferentiation of BPPCs in part by inhibiting p53 activation during biliary-mediated liver regeneration in zebrafish.

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来源期刊

Development 生物-发育生物学

CiteScore

6.70

自引率

4.30%

发文量

433

审稿时长

3 months

期刊介绍： Development’s scope covers all aspects of plant and animal development, including stem cell biology and regeneration. The single most important criterion for acceptance in Development is scientific excellence. Research papers (articles and reports) should therefore pose and test a significant hypothesis or address a significant question, and should provide novel perspectives that advance our understanding of development. We also encourage submission of papers that use computational methods or mathematical models to obtain significant new insights into developmental biology topics. Manuscripts that are descriptive in nature will be considered only when they lay important groundwork for a field and/or provide novel resources for understanding developmental processes of broad interest to the community. Development includes a Techniques and Resources section for the publication of new methods, datasets, and other types of resources. Papers describing new techniques should include a proof-of-principle demonstration that the technique is valuable to the developmental biology community; they need not include in-depth follow-up analysis. The technique must be described in sufficient detail to be easily replicated by other investigators. Development will also consider protocol-type papers of exceptional interest to the community. We welcome submission of Resource papers, for example those reporting new databases, systems-level datasets, or genetic resources of major value to the developmental biology community. For all papers, the data or resource described must be made available to the community with minimal restrictions upon publication. To aid navigability, Development has dedicated sections of the journal to stem cells & regeneration and to human development. The criteria for acceptance into these sections is identical to those outlined above. Authors and editors are encouraged to nominate appropriate manuscripts for inclusion in one of these sections.