The Loss of Chaf1a Affects the Proliferation and Differentiation of Hematopoietic Stem Progenitor Cells

Wanling You ； Ziliu Wang

《International Core Journal of Engineering》 8卷6期 (2022/06) Pp. 606-610

https://doi.org/10.6919/ICJE.202206_8(6).0082

摘要

Chaf1a is the p150 large subunit of chromatin assembly factor 1(CAF1), responsible for ligating the p60 subunits Chaf1b and p48 small subunits in CAF1,and interacting with PCNA in the process of DNA replication to promote H3-H4 dimer deposition in replication fork, which is the main function of CAF1.At present, a number of researches have studied the function of Chaf1a,including promoting the proliferation of human gastric cancer cells, regulating the cell cycle of human non-small cell lung cancer, repairing DNA damage caused by ROS, and regulating histone modification by recruiting epigenetic modifiers. However, the function of Chaf1a in hematopoietic system remains unclear. Therefore, this study modeled on mice specifically knocked out of Chaf1a in the hematopoietic system, aiming to investigate the role of Chaf1a in hematopoietic system. First, we constructed a mouse model of hematopoietic system-specific knockout of Chaf1a, inducing chaf1a 3 exon of mice to be knocked out with poly (I:C),and then sacrificed mice for analysis. We found that specific knockout of Chaf1a in the hematopoietic system did not affect lymphoid and myeloid differentiation of peripheral blood in mice. However, in vitro culture of mouse hematopoietic stem progenitor cells with methylcellulose medium found that knocking out chaf1a had fewer BFU-E than normal hematopoietic stem progenitor cells. Culture of LT through the Burk Culture experiment found that LT without Chaf1a had a decreased ability to proliferate in vitro. Therefore, we believe that Chaf1a plays an important regulatory role in the hematopoietic system of mice, and the specific regulatory mechanism needs to be further studied.

關鍵字

Chaf1a ； Hematopoietic Stem Cells ； Proliferation

參考文獻

Siminovitch L, M.E., Till JE, The distribution of colony-forming cells among spleen colonies. J Cell Comp Physiol, 1963. 62:327-36.

Kiel, M.J., et al., SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell, 2005. 121(7): p. 1109-21.

Morita, Y ., H. Ema, and H. Nakauchi, Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment. J Exp Med, 2010. 207(6): p. 1173-82.

Y amamoto, R., et al., Clonal analysis unveils self-renewing lineage-restricted progenitors generated directly from hematopoietic stem cells. Cell, 2013. 154(5): p. 1112-1126.

Groth, A., et al., Chromatin challenges during DNA replication and repair . Cell, 2007. 128(4): p. 721-733.