Schematic diagram depicting the function of Wdr5-mediated H3K4 methylation in HSPC improvement. Credit score: Prof. Liu’s group
A research led by Prof. Liu Feng from the Institute of Zoology of the Chinese language Academy of Sciences has recognized an important function for the tryptophan-aspartic acid (WD) repeat protein 5 (Wdr5) in sustaining the survival and genomic integrity of hematopoietic stem and progenitor cells (HSPCs) throughout embryonic improvement. The findings had been revealed within the Proceedings of the Nationwide Academy of Sciences.
HSPCs are the foundational “seed cells” of the blood system. They emerge within the aorta-gonad-mesonephros area throughout early embryogenesis and subsequently migrate to the caudal hematopoietic tissue, which is corresponding to the mammalian fetal liver. On this location, they bear speedy proliferation. Nevertheless, this intense replication part makes HSPCs prone to DNA harm and genomic instability.
On this research, utilizing zebrafish as a mannequin organism, the researchers found that Wdr5 capabilities as a genomic guardian by regulating a particular epigenetic mark—H3K4 methylation. When Wdr5 was disabled, the variety of HSPCs dropped considerably, resulting in widespread DNA harm and cell demise.
A key mechanistic perception is that Wdr5 reduces the buildup of “R-loops,” that are unstable DNA formations that may result in DNA harm. Moreover, within the absence of Wdr5, cells fail to activate the DNA harm response (DDR), a important restore pathway. Restoring DDR-related genes (resembling mlh1 and brip1) rescued the defects in HSPCs, underscoring Wdr5’s function in coordinating restore mechanisms.
This research is the primary to hyperlink H3K4 methylation to genome stability in HSPCs. The findings improve our understanding of HSPC improvement and should encourage new methods for regenerative drugs and coverings for blood problems.
Extra data:
Xiaohan Wang et al, Wdr5-mediated H3K4 methylation facilitates HSPC improvement through upkeep of genomic stability in zebrafish, Proceedings of the Nationwide Academy of Sciences (2025). DOI: 10.1073/pnas.2420534122
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Chinese language Academy of Sciences
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Zebrafish analysis highlights protein Wdr5’s function in stopping blood cell DNA harm (2025, March 25)
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