The Dynamic Expression Of CHD1L And Its Significance During Liver Development

Background and purposeCHD1L is a newly discovered oncogene which expressed specificly in liver cancer and there are no expression in normal adult liver. CHD1L encodes a protein with the same structure domain of SNF family and it indicates that CHD1L may have same functions on the regulation of nuclear protein receptor mediated genes transcription and cell growth as SNF family member do. But little is known about its exact roles and mechanism. The process of tumorigenesis possess several similar characteristics in cell proliferation, differentiation, and gene expression with embryonic development and indicates an internal links in embryonic development and tumorigenesis. Fetal liver is an excellent model for the study of the proliferation and differentiation of liver stem cells. The hematopoietic cells and stromal cells originated from mesoderm and endodermal epithelial cells will develope and become mature concomitantly in the microenvironment of fetal liver, but there were no issues about the expression and localization of CHD1L in this process and which have been subjected in this study. MethodsRT-PCR, Western blot and immunohistochemistry and immunofluorescence double-labeling methods were used to test the expression of CHD1L at mRNA and protein levels respectively during mouse fetal liver development. CHD1L expression was also verified in human fetal liver, placenta and hepatocarcinoma tissues, the cell types were determined.Results1. The expression of CHD1L in mouse fetal liver: The results of RT-PCR analysis have showed a dynamic expression of CHD1L during the development of mouse fetal liver . It will appear a weak CHD1L expression at E12.5 and arrive its peak time at E13.5-E15.5, after E16.5, the expression of CHD1L will decrease gradually and disappeared at E18.5. The expression of CHD1L weakened and vanished gradually along with the gradually enhanced expression of Albumin. The CHD1L positive cells can be found in the hepatic cord, hepatic sinusoid and sinusoidal endothelium of mouse fetal liver at day E13.5d-E15.5d by immunohistochemical staining. The positive cells in hepatic sinusoid and sinusoidal endothelium are majority cells. After day E15.5d, no CHD1L positive cells can be seen. CHD1L positive cells can also be found in human embryonic liver at 7wk-8wk, a corresponding time to the peak of CHD1L expression in mouse fetal liver. No positive cells can be found in 22wk-24wk human embryonic liver.2. The expression and identification of CHD1L in tissues of human placental villus. In human placental villi, the expression of CHD1L mRNA and protein are strong at 6wk-8wk, but decreased dramatically at 20wk-24wk. CHD1L positive cells were located at endovascular, vascular endothelial and mesenchymal in placenta villi. Two type cells include CHD1L~+/CD34~- and CHD1L~+/CD34~+ have been identified by immunofluorescent double staining method.The expression and identification of CHD1L in hepatocarcinoma tissues: In addition to the expression of CHD1L in carcinoma nest, CHD1L positive nuclei can also be found in the connective tissue around the cancer nest with oval or long rod shape. Immunofluorescent double staining result have shown that CHD1L positive cells in cancer nest are CHD1L~+/CD34~- , but there are two types of CHD1L positive cells include CHD1L~+/CD34~- and CHD1L~+/CD34~+ in the connective tissue around the cancer nest. No CHD1L positive cells in the vascular endothelial of cancer cell nest.Conclusions1. There is a dynamic CHD1L expression during mouse liver development and the expression will arrive at the peak at E13.5-E15.5d. The expression of CHD1L will decreased along with the maturation of hepatic cells which indicates that the expression of CHD1L has a closely relationship with the differentiation of hepatic cells.2. CHD1L expressed in mesoderm derived hematopoietic stem cells, embryonic endothelial cells and mesenchymal cells.3. The CHD1L positive cells located in hepatocarcinoma tissues may be the stem cells which have silenced and stayed in the liver during fetal development.