1.Establishment of a miniature porcine model for controlled cardiac deceased donor
Jianlong BI ; Ming CAI ; Qing YUAN ; Fan ZOU ; An HE
Chinese Journal of Organ Transplantation 2015;36(12):705-708
Objective To establish a type of porcine model for controlled Cardiac Deceased Donor.Method Using the wuzhishan miniature pig 2 ~ 4 months of age.After intravenous general anesthesia and respiratory,after open heart surgery to produce myocardial infarction model,to heartbeat stop completely,stop breathing machine and drug support,so we established a miniature pig cardiac death donor model.Record during the heart rate,systolic pressure,diastolic blood pressure,central venous blood pressure,blood oxygen saturation and regularly take on blood gas analysis.Before cardiac arrest,monitoring hemodynamic,blood gas analysis,and the time of death before the circulatory failure.After cardiac arrest respectively 0 min,15 min and 30 min,perfusion for donor organs (liver/kidney),get the pig's liver/kidney in the different time of the groups,observed the pathological changes of liver/kidney tissues by HE staining.Result The heartbeat stop completely occurs 7 ± 0.17 minutes after left descending coronary artery ligation and cease of assisted respiration in the different groups,systolic pressure,diastolic blood pressure,central venous pressure,blood oxygen saturation,CO2 partial pressure changed significantly;Immediately after cardiac arrest for compared group (0 min),schemia-reperfusion that group of 15 min after cardiac arrest injury is obvious,ischemia-reperfusion that group of 30 min after cardiac arrest injury is further.Conclusion Miniature pig donor model obtained in this method respiratory cycle failure stability,can be controlled,no adverse drug reactions,the organ ischemia-reperfusion injury caused by repetitive is better.
2.LIN28 coordinately promotes nucleolar/ribosomal functions and represses the 2C-like transcriptional program in pluripotent stem cells.
Zhen SUN ; Hua YU ; Jing ZHAO ; Tianyu TAN ; Hongru PAN ; Yuqing ZHU ; Lang CHEN ; Cheng ZHANG ; Li ZHANG ; Anhua LEI ; Yuyan XU ; Xianju BI ; Xin HUANG ; Bo GAO ; Longfei WANG ; Cristina CORREIA ; Ming CHEN ; Qiming SUN ; Yu FENG ; Li SHEN ; Hao WU ; Jianlong WANG ; Xiaohua SHEN ; George Q DALEY ; Hu LI ; Jin ZHANG
Protein & Cell 2022;13(7):490-512
LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Animals
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Cell Differentiation
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Embryo, Mammalian/metabolism*
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Embryonic Development
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Mice
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Pluripotent Stem Cells/metabolism*
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RNA, Messenger/genetics*
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RNA, Ribosomal
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RNA-Binding Proteins/metabolism*
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Transcription Factors/metabolism*
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Zygote/metabolism*