Systematic proteomics profiling of lysine crotonylation of the lung at Pseudoglandular and Canalicular phases in human fetus.

Lung tissue is an important organ of the fetus, and genomic research on its development has improved our understanding of the biology of this tissue. However, the proteomic research of developing fetal lung tissue is still very scarce. We conducted comprehensive analysis of two developmental stages of fetal lung tissue of proteomics. It showed the developmental characteristics of lung tissue, such as the down-regulation of metabolism-related protein expression, the up-regulation of cell cycle-related proteins, and the regulation in proteins and pathways related to lung development. In addition, we also discovered some key core proteins related to lung development, and provided some key crotonylation modification sites that regulation during lung tissue development. Our comprehensive analysis of lung proteomics can provide a more comprehensive understanding of the developmental status of lung tissue, and provide a certain reference for future research and epigenetics of lung tissue.

Prognostic value and immunological role of PTPN21 in pan-cancer analysis.

Introduction: At present, cancer remains a persistent public health challenge facing the whole world. Studies have found that PTPN21 is associated with the development of cancer. However, the prognostic potential of PTPN21 in pan-cancer remains unclear. In this work, we aimed to analyze the expression and prognostic value of PTPN21 in pan-cancer and to further study the relationship between PTPN21 and immune infiltration. Material and methods: TCGA and GEO data were used for expression and survival analysis. Genetic alterations in PTPN21 from TCGA cancer were studied in cBioPortal. TIMER2 was used to evaluate the correlation between PTPN21 expression and immune infiltration. The R packages "ggplot2" and "clusterProfiler" were used for GO and KEGG analysis. Results: PTPN21 was found to be a valuable diagnostic biomarker in multiple cancers, including bladder urothelial carcinoma (BLCA), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), and lung squamous cell carcinoma (LUSC). In addition, we observed that PTPN21 expression was associated with a variety of tumor mutations. Our results indicated a correlation between PTPN21 expression and immune infiltration. Enrichment analysis showed that PTPN21 was mainly involved in the regulation of neuroactive ligand-receptor interaction. Conclusions: Our study showed that PTPN21 expression is associated with clinical prognosis, mutation, and immune infiltration of tumors. PTPN21 may be a potential biomarker for many cancers, especially in KIRC.

Integrated single-cell analyses decode the developmental landscape of the human fetal spine.

The spine has essential roles in supporting body weight, and passaging the neural elements between the body and the brain. In this study, we used integrated single-cell RNA sequencing and single-cell transposase-accessible chromatin sequencing analyses to reveal the cellular heterogeneity, lineage, and transcriptional regulatory network of the developing human spine. We found that EPYC + HAPLN1+ fibroblasts with stem cell characteristics could differentiate into chondrocytes by highly expressing the chondrogenic markers SOX9 and MATN4. Neurons could originate from neuroendocrine cells, and MEIS2 may be an essential transcription factor that promotes spinal neural progenitor cells to selectively differentiate into neurons during early gestation. Furthermore, the interaction of NRP2_SEMA3C and CD74_APP between macrophages and neurons may be essential for spinal cord development. Our integrated map provides a blueprint for understanding human spine development in the early and midgestational stages at single-cell resolution and offers a tool for investigating related diseases.

Integrating spatial transcriptomics with single-cell transcriptomics reveals a spatiotemporal gene landscape of the human developing kidney.

BACKGROUND: Research on spatiotemporal gene landscape can provide insights into the spatial characteristics of human kidney development and facilitate kidney organoid cultivation. Here, we profiled the spatiotemporal gene programs of the human embryonic kidneys at 9 and 18 post-conception weeks (PCW) by integrating the application of microarray-based spatial transcriptomics and single-cell transcriptomics. RESULTS: We mapped transcriptomic signatures of scRNA-seq cell types upon the 9 and 18 PCW kidney sections based on cell-type deconvolution and multimodal intersection analyses, depicting a spatial landscape of developing cell subpopulations. We established the gene characteristics in the medullary regions and revealed a strong mitochondrial oxidative phosphorylation and glycolysis activity in the deeper medullary region. We also built a regulatory network centered on GDNF-ETV4 for nephrogenic niche development based on the weighted gene co-expression network analysis and highlighted the key roles of Wnt, FGF, and JAG1-Notch2 signaling in maintaining renal branching morphogenesis. CONCLUSIONS: Our findings obtained by this spatiotemporal gene program are expected to improve the current understanding of kidney development.

Differential Expression of lncRNA CASC2 in the Serum of Childhood Asthma and Its Role in Airway Smooth Muscle Cells Proliferation and Migration.

PURPOSE: Asthma is a common chronic disease in children. Abnormal expression of lncRNAs can be used as biomarkers for early diagnosis of asthma. The present study aimed to explore the expression change and clinical value of lncRNA CASC2 in asthma, and further investigate its potential mechanism. PATIENTS AND METHODS: Seventy asthma children and 66 healthy controls were recruited. Levels of mRNAs were detected using qRT-PCR. Receiver operating characteristic (ROC) curves were drawn for diagnostic value evaluation. Asthma cell models were established using PDGF-BB in Human airway smooth muscle cells (ASMCs). Levels of Th1/Th2 related cytokines were detected using ELISA. Lipofectamine 3000 was used for cell transfection. The target relationship was verified using luciferase activity assay. RESULTS: CASC2 was at a low level in asthma children in comparison with the healthy controls. Serum CASC2 can distinguish healthy individuals from asthma children. Overexpression of CASC2 inhibited PDGF-BB induced cell proliferation and migration. CASC2 upregulation inhibited the release of Th2 related cytokines (IL-4 and IL-10), but promoted the release of Th1-related cytokine (IFN-γ). In PDGF-BB treated ASMCs, the reduced expression of contractile phenotype marker (α-SMA) was detected, but the trend was reversed by CASC2 upregulation. LncRNA CASC2 serves as a ceRNA of miR-31-5p, overexpression of miR-31-5p reversed the influence of CASC2 on asthma in vitro. CONCLUSION: Serum CASC2 can distinguish healthy individuals from asthma children. CASC2 may be involved in childhood asthma through inhibiting ASMCs proliferation, migration and inflammation via sponging miR-31-5p.

Integrating Spatial Transcriptomics and Single-Cell RNA-seq Reveals the Gene Expression Profling of the Human Embryonic Liver.

The liver is one of vital organs of the human body, and it plays an important role in the metabolism and detoxification. Moreover, fetal liver is one of the hematopoietic places during ontogeny. Understanding how this complex organ develops during embryogenesis will yield insights into how functional liver replacement tissue can be engineered and how liver regeneration can be promoted. Here, we combine the advantages of single-cell RNA sequencing and Spatial Transcriptomics (ST) technology for unbiased analysis of fetal livers over developmental time from 8 post-conception weeks (PCW) and 17 PCW in humans. We systematically identified nine cell types, and defined the developmental pathways of the major cell types. The results showed that human fetal livers experienced blood rapid growth and immigration during the period studied in our experiments, and identified the differentially expressed genes, and metabolic changes in the developmental process of erythroid cells. In addition, we focus on the expression of liver disease related genes, and found that 17 genes published and linked to liver disease mainly expressed in megakaryocyte and endothelial, hardly expressed in any other cell types. Together, our findings provide a comprehensive and clear understanding of the differentiation processes of all main cell types in the human fetal livers, which may provide reference data and information for liver disease treatment and liver regeneration.