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 de-differentiation into bipotential progenitor cells (BPPCs), which subsequently re-differentiate into nascent hepatocytes and BECs to accomplish liver regeneration. However, the crucial factors governing the re-differentiation 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 with khdrbs1 in BECs, which caused defective liver regeneration and impaired re-differentiation of BPPCs. Furthermore, the khdrbs1-/- mutant displayed impaired proliferation and re-differentiation 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 conclude that Khdrbs1 promotes the re-differentiation of BPPCs in part by inhibiting p53 activation during biliary-mediated liver regeneration in zebrafish.
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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.
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