Background: Accumulating evidence suggests that the maxillary process, to which cranial crest cells migrate, is essential to tooth development. Emerging studies indicate that plays an essential role in odontogenesis. However, the underlying mechanisms have yet to be elucidated.
Aim: To establish the functionally heterogeneous population in the maxillary process, elucidate the effects of deficiency on gene expression differences.
Methods: p75NTR knockout () mice (from American Jackson laboratory) were used to collect the maxillofacial process tissue of p75NTR knockout mice, and the wild-type maxillofacial process of the same pregnant mouse wild was used as control. After single cell suspension, the cDNA was prepared by loading the single cell suspension into the 10x Genomics Chromium system to be sequenced by NovaSeq6000 sequencing system. Finally, the sequencing data in Fastq format were obtained. The FastQC software is used to evaluate the quality of data and CellRanger analyzed the data. The gene expression matrix is read by R software, and Seurat is used to control and standardize the data, reduce the dimension and cluster. We search for marker genes for subgroup annotation by consulting literature and database; explore the effect of p75NTR knockout on mesenchymal stem cells (MSCs) gene expression and cell proportion by cell subgrouping, differential gene analysis, enrichment analysis and protein-protein interaction network analysis; understand the interaction between MSCs cells and the differentiation trajectory and gene change characteristics of p75NTR knockout MSCs by cell communication analysis and pseudo-time analysis. Last we verified the findings single cell sequencing .
Results: We identified 21 cell clusters, and we re-clustered these into three subclusters. Importantly, we revealed the cell-cell communication networks between clusters. We clarified that was significantly associated with the regulation of mineralization.
Conclusion: This study provides comprehensive mechanistic insights into the maxillary- process-derived MSCs and demonstrates that is significantly associated with the odontogenesis in mesenchymal populations.
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http://dx.doi.org/10.4252/wjsc.v15.i6.589 | DOI Listing |
Background: Alzheimer's disease (AD) is the most common cause of dementia worldwide. It is characterized by dysfunction in the U1 small nuclear ribonucleoproteins (snRNPs) complex, which may precede TAU aggregation, enhancing premature polyadenylation, spliceosome dysfunction, and causing cell cycle reentry and death. Thus, we evaluated the effects of a synthetic single-stranded cDNA, called APT20TTMG, in induced pluripotent stem cells (iPSC) derived neurons from healthy and AD donors and in the Senescence Accelerated Mouse-Prone 8 (SAMP8) model.
View Article and Find Full Text PDFBackground: Immunotherapy of Alzheimer's disease (AD) is a promising approach to reducing the accumulation of beta-amyloid, a critical event in the onset of the disease. Targeting the group II metabotropic glutamate receptors, mGluR2 and mGluR3, could be important in controlling Aβ production, although their respective contribution remains unclear due to the lack of selective tools.
Method: 5xFAD mice were chronically treated by a brain penetrant camelid single domain antibody (VHH or nanobody) that is an activator of mGluR2.
Alzheimers Dement
December 2024
Columbia University Irving Medical Center, New York, NY, USA.
Background: Genetic studies indicate a causal role for microglia, the innate immune cells of the central nervous system (CNS), in Alzheimer's disease (AD). Despite the progress made in identifying genetic risk factors, such as CD33, and underlying molecular changes, there are currently limited treatment options for AD. Based on the immune-inhibitory function of CD33, we hypothesize that inhibition of CD33 activation may reverse microglial suppression and restore their ability to resolve inflammatory processes and mitigate pathogenic amyloid plaques, which may be neuroprotective.
View Article and Find Full Text PDFBackground: Our previous study identified that Sildenafil (a phosphodiesterase type 5 [PDE5] inhibitor) is a candidate repurposable drug for Alzheimer's Disease (AD) using in silico network medicine approach. However, the clinically meaningful size and mechanism-of-actions of sildenafil in potential prevention and treatment of AD remind unknown.
Method: We conducted new patient data analyses using both the MarketScan® Medicare with Supplemental database (n = 7.
Alzheimers Dement
December 2024
NYU Grossman School of Medicine, New York, NY, USA; NYU, New York City, NY, USA.
Background: Astrocytes, a major glial cell in the central nervous system (CNS), can become reactive in response to inflammation or injury, and release toxic factors that kill specific subtypes of neurons. Over the past several decades, many groups report that reactive astrocytes are present in the brains of patients with Alzheimer's disease, as well as several other neurodegenerative diseases. In addition, reactive astrocyte sub-types most associated with these diseases are now reported to be present during CNS cancers of several types.
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