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Journal of Atherosclerosis and... Sep 2023There are still many patients suffering from ischemic stroke and related disabilities worldwide. To develop a treatment that promotes functional recovery after acute... (Review)
Review
There are still many patients suffering from ischemic stroke and related disabilities worldwide. To develop a treatment that promotes functional recovery after acute ischemic stroke, we need to elucidate endogenous tissue repair mechanisms. The concept of a neurovascular unit (NVU) indicates the importance of a complex orchestration of cell-cell interactions and their microenvironment in the physiology and pathophysiology of various central nervous system diseases, particularly ischemic stroke. In this concept, microvascular pericytes play a crucial role in regulating the blood-brain barrier integrity, cerebral blood flow (CBF), and vascular stability. Recent evidence suggests that pericytes are also involved in the tissue repair leading to functional recovery following acute ischemic stroke through the interaction with other cell types constituting the NVU; pericytes may organize CBF recovery, macrophage-mediated clearance of myelin debris, intrainfarct fibrosis, and periinfarct astrogliosis and remyelination. In this review, we will discuss the physiological and pathophysiological functions of pericytes, their involvement in the molecular mechanisms underlying tissue repair and functional recovery after ischemic stroke, and a therapeutic strategy to promote endogenous regeneration.
Topics: Humans; Pericytes; Ischemic Stroke; Stroke; Blood-Brain Barrier; Macrophages
PubMed: 37394570
DOI: 10.5551/jat.RV22007 -
Nature Medicine Dec 2023Pregnancy loss is often caused by chromosomal abnormalities of the conceptus. The prevalence of these abnormalities and the allocation of (ab)normal cells in embryonic...
Pregnancy loss is often caused by chromosomal abnormalities of the conceptus. The prevalence of these abnormalities and the allocation of (ab)normal cells in embryonic and placental lineages during intrauterine development remain elusive. In this study, we analyzed 1,745 spontaneous pregnancy losses and found that roughly half (50.4%) of the products of conception (POCs) were karyotypically abnormal, with maternal and paternal age independently contributing to the increased genomic aberration rate. We applied genome haplarithmisis to a subset of 94 pregnancy losses with normal parental and POC karyotypes. Genotyping of parental DNA as well as POC extra-embryonic mesoderm and chorionic villi DNA, representing embryonic and trophoblastic tissues, enabled characterization of the genomic landscape of both lineages. Of these pregnancy losses, 35.1% had chromosomal aberrations not previously detected by karyotyping, increasing the rate of aberrations of pregnancy losses to 67.8% by extrapolation. In contrast to viable pregnancies where mosaic chromosomal abnormalities are often restricted to chorionic villi, such as confined placental mosaicism, we found a higher degree of mosaic chromosomal imbalances in extra-embryonic mesoderm rather than chorionic villi. Our results stress the importance of scrutinizing the full allelic architecture of genomic abnormalities in pregnancy loss to improve clinical management and basic research of this devastating condition.
Topics: Pregnancy; Female; Humans; Placenta; Pregnancy Trimester, First; Abortion, Spontaneous; Prevalence; Chromosome Aberrations; Mosaicism; DNA
PubMed: 37996709
DOI: 10.1038/s41591-023-02645-5 -
Science Advances Jan 2024Spatiotemporal patterns widely occur in biological, chemical, and physical systems. Particularly, embryonic development displays a diverse gamut of repetitive patterns... (Review)
Review
Spatiotemporal patterns widely occur in biological, chemical, and physical systems. Particularly, embryonic development displays a diverse gamut of repetitive patterns established in many tissues and organs. Branching treelike structures in lungs, kidneys, livers, pancreases, and mammary glands as well as digits and bones in appendages, teeth, and palates are just a few examples. A fascinating instance of repetitive patterning is the sequential segmentation of the primary body axis, which is conserved in all vertebrates and many arthropods and annelids. In these species, the body axis elongates at the posterior end of the embryo containing an unsegmented tissue. Meanwhile, segments sequentially bud off from the anterior end of the unsegmented tissue, laying down an exquisite repetitive pattern and creating a segmented body plan. In vertebrates, the paraxial mesoderm is sequentially divided into somites. In this review, we will discuss the most prominent models, the most puzzling experimental data, and outstanding questions in vertebrate somite segmentation.
Topics: Animals; Body Patterning; Somites; Mesoderm; Vertebrates; Embryonic Development; Gene Expression Regulation, Developmental
PubMed: 38277458
DOI: 10.1126/sciadv.adk8937 -
BioRxiv : the Preprint Server For... Oct 2023During heart development, a well-characterized network of transcription factors initiates cardiac gene expression and defines the precise timing and location of cardiac...
During heart development, a well-characterized network of transcription factors initiates cardiac gene expression and defines the precise timing and location of cardiac progenitor specification. However, our understanding of the post-initiation transcriptional events that regulate cardiac gene expression is still incomplete. The PAF1C component Rtf1 is a transcription regulatory protein that modulates pausing and elongation of RNA Pol II, as well as cotranscriptional histone modifications. Here we report that Rtf1 is essential for cardiogenesis in fish and mammals, and that in the absence of Rtf1 activity, cardiac progenitors arrest in an immature state. We found that Rtf1's Plus3 domain, which confers interaction with the transcriptional pausing and elongation regulator Spt5, was necessary for cardiac progenitor formation. ChIP-seq analysis further revealed changes in the occupancy of RNA Pol II around the transcription start site (TSS) of cardiac genes in morphants reflecting a reduction in transcriptional pausing. Intriguingly, inhibition of pause release in morphants and mutants restored the formation of cardiac cells and improved Pol II occupancy at the TSS of key cardiac genes. Our findings highlight the crucial role that transcriptional pausing plays in promoting normal gene expression levels in a cardiac developmental context.
PubMed: 37873297
DOI: 10.1101/2023.10.13.562296 -
Frontiers in Bioscience (Landmark... Apr 2024Pericytes, a specific type of mesenchymal cell that surround the basement membrane of pulmonary venules and capillaries. They are crucial pathological features observed... (Review)
Review
Pericytes, a specific type of mesenchymal cell that surround the basement membrane of pulmonary venules and capillaries. They are crucial pathological features observed in individuals with the severe lung disease of pulmonary fibrosis (PF). The presence of pericytes leads to inflammation and fibrosis in the lung interstitium and alveolar space due to the release of various cytokines and chemokines. Pericytes also stimulate the proliferation and activation of fibroblasts, thereby promoting the progression of PF. Previous studies examining the mechanism of action of pericytes have primarily focused on cell signal transduction pathways, cell growth and death processes, and the synthesis and breakdown of extracellular matrix (ECM). Notably, the transforming growth factor-β (TGF-β) and Wnt signaling pathways have been associated with the action of pericytes in driving the progression of PF. It is therefore clear that pericytes play an essential role in the development of PF, while also offering possible avenues for targeted therapeutic intervention against this condition. The current article provides a comprehensive review on how pericytes contribute to inflammatory responses, as well as their importance for understanding the mechanism of PF. In addition, this review discusses the potential use of pericyte-targeted approaches for the treatment of patients affected by this debilitating lung disease.
Topics: Pericytes; Humans; Pulmonary Fibrosis; Animals; Transforming Growth Factor beta; Signal Transduction; Extracellular Matrix; Wnt Signaling Pathway
PubMed: 38682199
DOI: 10.31083/j.fbl2904141 -
Frontiers in Zoology Jan 2024Early during onychophoran development and prior to the formation of the germ band, a posterior tissue thickening forms the posterior pit. Anterior to this thickening...
BACKGROUND
Early during onychophoran development and prior to the formation of the germ band, a posterior tissue thickening forms the posterior pit. Anterior to this thickening forms a groove, the embryonic slit, that marks the anterior-posterior orientation of the developing embryo. This slit is by some authors considered the blastopore, and thus the origin of the endoderm, while others argue that the posterior pit represents the blastopore. This controversy is of evolutionary significance because if the slit represents the blastopore, then this would support the amphistomy hypothesis that suggests that a slit-like blastopore in the bilaterian ancestor evolved into protostomy and deuterostomy.
RESULTS
In this paper, we summarize our current knowledge about endoderm and mesoderm development in onychophorans and provide additional data on early endoderm- and mesoderm-determining marker genes such as Blimp, Mox, and the T-box genes.
CONCLUSION
We come to the conclusion that the endoderm of onychophorans forms prior to the development of the embryonic slit, and thus that the slit is not the primary origin of the endoderm. It is thus unlikely that the embryonic slit represents the blastopore. We suggest instead that the posterior pit indeed represents the lips of the blastopore, and that the embryonic slit (and surrounding tissue) represents a morphologically superficial archenteron-like structure. We conclude further that both endoderm and mesoderm development are under control of conserved gene regulatory networks, and that many of the features found in arthropods including the model Drosophila melanogaster are likely derived.
PubMed: 38267986
DOI: 10.1186/s12983-024-00521-7 -
Indian Journal of Ophthalmology May 2024The caruncle is a unique anatomical site in the human body, comprising various structures derived from the surface ectoderm and mesoderm. Caruncular lesions can range...
PURPOSE
The caruncle is a unique anatomical site in the human body, comprising various structures derived from the surface ectoderm and mesoderm. Caruncular lesions can range from benign to malignant and present challenges in accurate diagnosis and timely management due to their hidden nature and proximity to the lacrimal sac. This study aims to provide a comprehensive description of caruncular lesions, presenting the first Indian case series on this topic.
METHODS
Ethical approval was obtained, and data collection was conducted at a tertiary care center in India. A retrospective analysis was performed on 44 patients with caruncular lesions treated between 2013 and 2020. Detailed patient histories, clinical examinations, slit lamp imaging, and excision biopsies were conducted. Histopathological examination of the specimens was carried out.
RESULTS
The study included 42 cases of caruncular lesions, with a mean age of 31.09 years. The majority of cases were male (54.54%). Benign lesions accounted for 84.09% of the cases, while premalignant and malignant lesions accounted for 11.36% and 4.54%, respectively. Papilloma and nevus were the most common lesions, with 11 cases each. All caruncular lesions were successfully and completely excised without complications. Histopathological examination confirmed the accuracy of the diagnoses, with an 84.09% concordance rate between clinical assessment and pathological diagnosis.
CONCLUSION
This case series reveals a predominance of benign lesions among individuals in their early thirties. The successful excision of all lesions with a high concordance rate between clinical assessment and histopathological diagnosis underscores the importance of timely and accurate management.
PubMed: 38770617
DOI: 10.4103/IJO.IJO_2088_23 -
Stem Cell Reports Oct 2023The formation of vascular structures is fundamental for in vitro tissue engineering. Vascularization can enable the nutrient supply within larger structures and...
The formation of vascular structures is fundamental for in vitro tissue engineering. Vascularization can enable the nutrient supply within larger structures and increase transplantation efficiency. We differentiated human induced pluripotent stem cells toward endothelial cells in 3D suspension culture. To investigate in vitro neovascularization and various 3D microenvironmental approaches, we designed a comprehensive single-cell transcriptomic study. Time-resolved single-cell transcriptomics of the endothelial and co-evolving mural cells gave insights into cell type development, stability, and plasticity. Transfer to a 3D hydrogel microenvironment induced neovascularization and facilitated tracing of migrating, coalescing, and tubulogenic endothelial cell states. During maturation, we monitored two pericyte subtypes evolving mural cells. Profiling cell-cell interactions between pericytes and endothelial cells revealed angiogenic signals during tubulogenesis. In silico discovered ligands were tested for their capability to attract endothelial cells. Our data, analyses, and results provide an in vitro roadmap to guide vascularization in future tissue engineering.
Topics: Humans; Endothelial Cells; Induced Pluripotent Stem Cells; Neovascularization, Physiologic; Coculture Techniques; Neovascularization, Pathologic; Pericytes
PubMed: 37714147
DOI: 10.1016/j.stemcr.2023.08.008