Despite extensive research on osteoblast differentiation and proliferation in mesenchymal stem cells (MSCs), the accurate mechanism remains to be further elucidated. MicroRNAs have been reported to be key regulators of osteoblast differentiation and proliferation. Here, we found that miR‐144‐3p is down‐regulated during osteoblast differentiation of C3H10T1/2 cells. Overexpression of miR‐144‐3p inhibited osteogenic differentiation, whereas inhibition of miR‐144‐3p reversed this process. Furthermore, miR‐144‐3p inhibited the proliferation of C3H10T1/2 cells by arresting cells at the G0/G1 phase. Results from bioinformatics analysis, luciferase assay and western blotting demonstrated that miR‐144‐3p directly targeted Smad4. Additionally, Smad4 knockdown blocks the effects of miR‐144‐3p inhibitor. Therefore, we conclude that miR‐144‐3p negatively regulates osteogenic differentiation and proliferation of C3H10T1/2 cells by targeting Smad4.
Labor is initiated as a result of hormonal changes that are induced by the activation of the inflammatory response and a series of biochemical events. The amnion, which is the primary source of prostaglandin E2 (PGE2), plays an important role in the process of labor. In the present study, we uncovered a pathway in which c-fos, cyclooxygenase-2 (COX2) and miR-144 function as hormonal modulators in the amnions of pregnant mice and humans. miR-144 down-regulated the synthesis of PGE2 during pregnancy by directly and indirectly inhibiting COX2 expression and by directly inhibiting the expression of c-fos, a transcriptional activator of COX2 and miR-144. Estrogen (E2) activated c-fos, thus promoting the expression of miR-144 and COX2 during labor. However, the increase in COX2 resulted in the partial inhibition of COX2 expression by miR-144, thereby slightly reducing the secretion of PGE2. These observations suggest that miR-144 inhibits PGE2 secretion by section to prevent the initiation of premature labor. Up-regulated expression of miR-144, c-fos and COX2 was also observed both in preterm mice and in mice undergoing normal labor. In summary, miR-144, c-fos and COX2 play important roles in regulating PGE2 secretion in the amnion during pregnancy and labor.
Motivation
Rapid developments of single cell RNA sequencing technologies allow study of responses to external perturbations at individual cell level. However, in many cases, it is hard to collect the perturbed cells, such as knowing the response of a cell type to the drug before actual medication to a patient. Prediction in silicon could alleviate the problem and save cost. Although several tools have been developed, their prediction accuracy leaves much room for improvement.
Results
In this paper, we propose scPreGAN, a deep generative model for predicting the response of single cell expression to perturbation. ScPreGAN integrates autoencoder and generative adversarial network, the former is to extract common information of the unperturbed data and the perturbed data, the latter is to predict the perturbed data. Experiments on three real datasets show that scPreGAN outperforms three state-of-the-art methods, which can capture the complicated distribution of cell expression and generate the prediction data with the same expression abundance as the real data.
Availability and implementation
The implementation of scPreGAN is available via https://github.com/JaneJiayiDong/scPreGAN. To reproduce the results of this article, please visit https://github.com/JaneJiayiDong/scPreGAN-reproducibility.
Supplementary information
Supplementary data are available at Bioinformatics online.
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