ZKSCAN3 slows the aging of human stem cells

ZKSCAN3 is one of the members of the zinc finger protein family with SCAN domain and has been reported as a transcription regulator to inhibit the expression of autophagy-related genes. However, the current international research on ZKSCAN3 is mainly based on tumor cell line and model animals, its biological function in normal human stem cells and other secondary cells is not clear.
May 19, the Qu Jing Research Group of the Institute of Zoology of the Chinese Academy of Sciences, The Liu Guanghui Research Group and the Zhang Weiwei Research Group of the Beijing Genomics Research Institute of the Chinese Academy of Sciences collaborated to publish the latest research results online in
magazine. The study first reported that ZKSCAN3 slows the aging of human stem cells by autophagy non-dependent. In terms of mechanism, ZKSCAN3 enhances genomic stability and inhibits the expression of duplicate components by stabilizing the interaction between the nucleoglobin and isochromatin.
In the study, the researchers first found that ZKSCAN3 showed a downward expression in human pre-aging-filled stem cells, replicated aging interstitined stem cells, and primary intergenerational charged stem cells isolated by older individuals, suggesting a potential link between ZKSCAN3 and aging regulation. Using CRISPR/Cas9-mediated gene editing technology and stem cell-directed induction differentiation, the researchers obtained for the first time human embryonic stem cells and interstate stem cells that target ZKSCAN3. Although the absence of ZKSCAN3 does not affect the self-renewal and differentiation of human embryonic stem cells, the human-filled stem cells knocked out by ZKSCAN3 are shown as esopes that accelerate aging.
researchers further discovered that ZKSCAN3 can interact with nucleoglobin and isochrome proteins by integrating multi-level histological analysis such as interacting protein spectrometry, chromosomal immunopopulation sequencing, chromatin access sequencing, DNA adenine methyl transferase intersequencing, and RNA sequencing. The absence of ZKSCAN3 leads to the weakening of the interaction between nuclear membrane proteins and genomes in human-charged stem cells, the loss of isochromatin, and the elevation of transcription levels of genome repetitive elements, which eventually induces the aging of human-filled stem cells. It is worth noting that over-expression of ZKSCAN3 or activation of endogenetic ZKSCAN3 expression through crispRa system can delay the aging of human-filled stem cells.
this study reveals for the first time the new functions and mechanisms of ZKSCAN3 as an appearance regulatory factor to regulate the steady state of human stem cells and inhibit their aging. This discovery expands people's understanding of the new function of zinc finger protein family, deepens the understanding of the presumed genetic mechanism of aging, and provides important clues and ideas for delaying stem cell aging and preventing aging-related diseases. (Source: Zhang Qingdan, China Science Daily)
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