Forskolin-driven conversion of human somatic cells into induced neurons through regulation of the cAMP-CREB1-JNK signaling.

Human somatic cells can be reprogrammed into neuron cell fate through regulation of a single transcription factor or application of small molecule cocktails. Methods: Here, we report that forskolin efficiently induces the conversion of human somatic cells into induced neurons (FiNs). Results: A large population of neuron-like phenotype cells was observed as early as 24-36 h post-induction. There were >90% TUJ1-, >80% MAP2-, and >80% NEUN-positive neurons at 5 days post-induction. Multiple subtypes of neurons were present among TUJ1-positive cells, including >60% cholinergic, >20% glutamatergic, >10% GABAergic, and >5% dopaminergic neurons. FiNs exhibited typical neural electrophysiological activity in vitro and the ability to survive in vitro and in vivo more than 2 months. Mechanistically, forskolin functions in FiN reprogramming by regulating the cAMP-CREB1-JNK signals, which upregulates cAMP-CREB1 expression and downregulates JNK expression. Conclusion: Overall, our studies identify a safer and efficient single-small-molecule-driven reprogramming approach for induced neuron generation and reveal a novel regulatory mechanism of neuronal cell fate acquisition.

Long-chain noncoding RNA sequencing analysis reveals the molecular profiles of chemically induced mammary epithelial cells.

Long noncoding RNAs (lncRNAs) were important regulators affecting the cellular reprogramming process. Previous studies from our group have demonstrated that small molecule compounds can induce goat ear fibroblasts to reprogram into mammary epithelial cells with lactation function. In this study, we used lncRNA-Sequencing (lncRNA-seq) to analyze the lncRNA expression profile of cells before and after reprogramming (CK vs. 5i8 d). The results showed that a total of 3,970 candidate differential lncRNAs were detected, 1,170 annotated and 2,800 new lncRNAs. Compared to 0 d cells, 738 lncRNAs were significantly upregulated and 550 were significantly downregulated in 8 d cells. Heat maps of lncrnas and target genes with significant differences showed that the fate of cell lineages changed. Functional enrichment analysis revealed that these differently expressed (DE) lncRNAs target genes were mainly involved in signaling pathways related to reprogramming and mammary gland development, such as the Wnt signaling pathway, PI3K-Akt signaling pathway, arginine and proline metabolism, ECM-receptor interaction, and MAPK signaling pathway. The accuracy of sequencing was verified by real-time fluorescence quantification (RT-qPCR) of lncRNAs and key candidate genes, and it was also demonstrated that the phenotype and genes of the cells were changed. Therefore, this study offers a foundation for explaining the molecular mechanisms of lncRNAs in chemically induced mammary epithelial cells.

[Biogeochemical processes of the major ions and dissolved inorganic carbon in the Guijiang River].

Within the drainage basin, information about natural processes and human activities can be recorded in the chemical composition of riverine water. The analysis of the Guijiang River, the first level tributary of the Xijiang River, demonstrated that the chemical composition of water in the Guijiang River was mainly influenced by the chemical weathering of carbonate rocks within the drainage basin, in which CO2 was the main erosion medium, and that the weathering of carbonate rock by H2SO4 had a remarkable impact on the water chemical composition in the Guijiang River. Precipitation, human activities, the weathering of carbonate rocks and silicate rocks accounted for 2.7%, 6.3%, 72.8% and 18.2% of the total dissolved load, respectively. The stable isotopic compositions of dissolved inorganic carbon (delta13C(DIC)) indicated that DIC in the Guijiang River had been assimilated by the phytoplankton in photosynthesis. The primary production of phytoplankton contributed to 22.3%-30.9% of particulate organic carbon (POC) in the Guijiang River, which implies that phytoplankton can transform DIC into POC by photosynthesis, and parts of POC will sink into the bottom of the river in transit, which leads into the formation of burial organic carbon.