Tonghua Liu: A life dedicated to clinical pathology


FBXW7 E3 ubiquitin ligase: degrading, not degrading, or being degraded


Ubiquitin is double-phosphorylated by PINK1 for enhanced pH-sensitivity of conformational switch


Core transcriptional signatures of phase change in the migratory locust

ABSTRACT

Phenotypic plasticity plays fundamental roles in successful adaptation of animals in response to environmental variations. Here, to reveal the transcriptome reprogramming in locust phase change, a typical phenotypic plasticity, we conducted a comprehensive analysis of multiple phase-related transcriptomic datasets of the migratory locust. We defined PhaseCore genes according to their contribution to phase differentiation by the adjustment for confounding principal components analysis algorithm (AC-PCA). Compared with other genes, PhaseCore genes predicted phase status with over 87.5% accuracy and displayed more unique gene attributes including the faster evolution rate, higher CpG content and higher specific expression level. Then, we identified 20 transcription factors (TFs) named PhaseCoreTF genes that are associated with the regulation of PhaseCore genes. Finally, we experimentally verified the regulatory roles of three representative TFs (Hr4, Hr46, and grh) in phase change by RNAi. Our findings revealed that core transcriptional signatures are involved in the global regulation of locust phase changes, suggesting a potential common mechanism underlying phenotypic plasticity in insects. The expression and network data are accessible in an online resource called LocustMine (http://www.locustmine.org:8080/locustmine).

Genetic evidence for asymmetric blocking of higher-order chromatin structure by CTCF/cohesin


Lipid droplets and mitochondria are anchored during brown adipocyte differentiation


JMJD3 in the regulation of human diseases

ABSTRACT

In recent years, many studies have shown that histone methylation plays an important role in maintaining the active and silent state of gene expression in human diseases. The Jumonji domain-containing protein D3 (JMJD3), specifically demethylate di- and trimethyl-lysine 27 on histone H3 (H3K27me2/3), has been widely studied in immune diseases, infectious diseases, cancer, developmental diseases, and aging related diseases. We will focus on the recent advances of JMJD3 function in human diseases, and looks ahead to the future of JMJD3 gene research in this review.

Continuous culture of urine-derived bladder cancer cells for precision medicine


Domesticated cynomolgus monkey embryonic stem cells allow the generation of neonatal interspecies chimeric pigs

Abstract

Blastocyst complementation by pluripotent stem cell (PSC) injection is believed to be the most promising method to generate xenogeneic organs. However, ethical issues prevent the study of human chimeras in the late embryonic stage of development. Primate embryonic stem cells (ESCs), which have similar pluripotency to human ESCs, are a good model for studying interspecies chimerism and organ generation. However, whether primate ESCs can be used in xenogenous grafts remains unclear. In this study, we evaluated the chimeric ability of cynomolgus monkey (Macaca fascicularis) ESCs (cmESCs) in pigs, which are excellent hosts because of their many similarities to humans. We report an optimized culture medium that enhanced the anti-apoptotic ability of cmESCs and improved the development of chimeric embryos, in which domesticated cmESCs (D-ESCs) injected into pig blastocysts differentiated into cells of all three germ layers. In addition, we obtained two neonatal interspecies chimeras, in which we observed tissue-specific D-ESC differentiation. Taken together, the results demonstrate the capability of D-ESCs to integrate and differentiate into functional cells in a porcine model, with a chimeric ratio of 0.001–0.0001 in different neonate tissues. We believe this work will facilitate future developments in xenogeneic organogenesis, bringing us one step closer to producing tissue-specific functional cells and organs in a large animal model through interspecies blastocyst complementation.