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Trends in Cell Biology Jan 2024Pericytes are known as the mural cells in small-caliber vessels that interact closely with the endothelium. Pericytes play a key role in vasculature formation and... (Review)
Review
Pericytes are known as the mural cells in small-caliber vessels that interact closely with the endothelium. Pericytes play a key role in vasculature formation and homeostasis, and when dysfunctional contribute to vasculature-related diseases such as diabetic retinopathy and neurodegenerative conditions. In addition, significant extravascular roles of pathological pericytes are being discovered with relevant implications for cancer and fibrosis. Pericyte research is challenged by the lack of consistent molecular markers and clear discrimination criteria versus other (mural) cells. However, advances in single-cell approaches are uncovering and clarifying mural cell identities, biological functions, and ontogeny across organs. We discuss the latest developments in pericyte pathobiology to inform future research directions and potential outcomes.
Topics: Humans; Pericytes; Biomarkers; Endothelium, Vascular; Homeostasis
PubMed: 37474376
DOI: 10.1016/j.tcb.2023.06.001 -
The Journal of Clinical Investigation Jul 2023Mesenchymal cells are uniquely located at the interface between the epithelial lining and the stroma, allowing them to act as a signaling hub among diverse cellular... (Review)
Review
Mesenchymal cells are uniquely located at the interface between the epithelial lining and the stroma, allowing them to act as a signaling hub among diverse cellular compartments of the lung. During embryonic and postnatal lung development, mesenchyme-derived signals instruct epithelial budding, branching morphogenesis, and subsequent structural and functional maturation. Later during adult life, the mesenchyme plays divergent roles wherein its balanced activation promotes epithelial repair after injury while its aberrant activation can lead to pathological remodeling and fibrosis that are associated with multiple chronic pulmonary diseases, including bronchopulmonary dysplasia, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease. In this Review, we discuss the involvement of the lung mesenchyme in various morphogenic, neomorphogenic, and dysmorphogenic aspects of lung biology and health, with special emphasis on lung fibroblast subsets and smooth muscle cells, intercellular communication, and intrinsic mesenchymal mechanisms that drive such physiological and pathophysiological events throughout development, homeostasis, injury repair, regeneration, and aging.
Topics: Infant, Newborn; Humans; Lung; Pulmonary Disease, Chronic Obstructive; Fibrosis; Regeneration; Mesoderm; Epithelial Cells
PubMed: 37463440
DOI: 10.1172/JCI170498 -
Differentiation; Research in Biological... Nov 2023FGF18 was discovered in 1998. It is a pleiotropic growth factor that stimulates major signalling pathways involved in cell proliferation and growth, and is involved in...
FGF18 was discovered in 1998. It is a pleiotropic growth factor that stimulates major signalling pathways involved in cell proliferation and growth, and is involved in the development and homeostasis of many tissues such as bone, lung, and central nervous system. The gene consists of five exons that code for a 207 amino acid glycosylated protein. FGF18 is widely expressed in developing and adult chickens, mice, and humans, being seen in the mesenchyme, brain, skeleton, heart, and lungs. Knockout studies of FGF18 in mice lead to perinatal death, characterised by distinct phenotypes such as cleft palate, smaller body size, curved long bones, deformed ribs, and reduced crania. As can be expected from a protein involved in so many functions FGF18 is associated with various diseases such as idiopathic pulmonary fibrosis, congenital diaphragmatic hernia, and most notably various types of cancer such as breast, lung, and ovarian cancer.
PubMed: 38007374
DOI: 10.1016/j.diff.2023.10.003 -
Pharmaceuticals (Basel, Switzerland) Sep 2023Cellular therapy has used mesenchymal stem cells (MSCs), which in cell culture are multipotent progenitors capable of producing a variety of cells limited to the... (Review)
Review
Cellular therapy has used mesenchymal stem cells (MSCs), which in cell culture are multipotent progenitors capable of producing a variety of cells limited to the mesoderm layer. There are two types of MSC sources: (1) adult MSCs, which are obtained from bone marrow, adipose tissue, peripheral blood, and dental pulp; and (2) neonatal-tissue-derived MSCs, obtained from extra-embryonic tissues such as the placenta, amnion, and umbilical cord. Until April 2023, 1120 registered clinical trials had been using MSC therapies worldwide, but there are only 12 MSC therapies that have been approved by regulatory agencies for commercialization. Nine of the twelve MSC-approved products are from Asia, with Republic of Korea being the country with the most approved therapies. In the future, MSCs will play an important role in the treatment of many diseases. However, there are many issues to deal with before their application and usage in the medical field. Some strategies have been proposed to face these problems with the hope of reaching the objective of applying these MSC therapies at optimal therapeutic levels.
PubMed: 37765141
DOI: 10.3390/ph16091334 -
Nature Oct 2023Clostridioides difficile infection (CDI) is a major cause of healthcare-associated gastrointestinal infections. The exaggerated colonic inflammation caused by...
Clostridioides difficile infection (CDI) is a major cause of healthcare-associated gastrointestinal infections. The exaggerated colonic inflammation caused by C. difficile toxins such as toxin B (TcdB) damages tissues and promotes C. difficile colonization, but how TcdB causes inflammation is unclear. Here we report that TcdB induces neurogenic inflammation by targeting gut-innervating afferent neurons and pericytes through receptors, including the Frizzled receptors (FZD1, FZD2 and FZD7) in neurons and chondroitin sulfate proteoglycan 4 (CSPG4) in pericytes. TcdB stimulates the secretion of the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) from neurons and pro-inflammatory cytokines from pericytes. Targeted delivery of the TcdB enzymatic domain, through fusion with a detoxified diphtheria toxin, into peptidergic sensory neurons that express exogeneous diphtheria toxin receptor (an approach we term toxogenetics) is sufficient to induce neurogenic inflammation and recapitulates major colonic histopathology associated with CDI. Conversely, mice lacking SP, CGRP or the SP receptor (neurokinin 1 receptor) show reduced pathology in both models of caecal TcdB injection and CDI. Blocking SP or CGRP signalling reduces tissue damage and C. difficile burden in mice infected with a standard C. difficile strain or with hypervirulent strains expressing the TcdB2 variant. Thus, targeting neurogenic inflammation provides a host-oriented therapeutic approach for treating CDI.
Topics: Animals; Mice; Bacterial Toxins; Calcitonin Gene-Related Peptide; Clostridioides difficile; Clostridium Infections; Neurogenic Inflammation; Pericytes; Receptors, Neurokinin-1; Substance P; Neurons, Afferent; Inflammation Mediators; Cecum; Signal Transduction
PubMed: 37699522
DOI: 10.1038/s41586-023-06607-2 -
Cell Research Sep 2023Studies of cultured embryos have provided insights into human peri-implantation development. However, detailed knowledge of peri-implantation lineage development as well...
Studies of cultured embryos have provided insights into human peri-implantation development. However, detailed knowledge of peri-implantation lineage development as well as underlying mechanisms remains obscure. Using 3D-cultured human embryos, herein we report a complete cell atlas of the early post-implantation lineages and decipher cellular composition and gene signatures of the epiblast and hypoblast derivatives. In addition, we develop an embryo-like assembloid (E-assembloid) by assembling naive hESCs and extraembryonic cells. Using human embryos and E-assembloids, we reveal that WNT, BMP and Nodal signaling pathways synergistically, but functionally differently, orchestrate human peri-implantation lineage development. Specially, we dissect mechanisms underlying extraembryonic mesoderm and extraembryonic endoderm specifications. Finally, an improved E-assembloid is developed to recapitulate the epiblast and hypoblast development and tissue architectures in the pre-gastrulation human embryo. Our findings provide insights into human peri-implantation development, and the E-assembloid offers a useful model to disentangle cellular behaviors and signaling interactions that drive human embryogenesis.
Topics: Humans; Germ Layers; Embryo, Mammalian; Embryo Implantation; Endoderm; Mesoderm; Embryonic Development
PubMed: 37460804
DOI: 10.1038/s41422-023-00846-8 -
Cells Jul 2023Pericytes are specialized cells located in close proximity to endothelial cells within the microvasculature. They play a crucial role in regulating blood flow,... (Review)
Review
Pericytes are specialized cells located in close proximity to endothelial cells within the microvasculature. They play a crucial role in regulating blood flow, stabilizing vessel walls, and maintaining the integrity of the blood-brain barrier. The loss of pericytes has been associated with the development and progression of various diseases, such as diabetes, Alzheimer's disease, sepsis, stroke, and traumatic brain injury. This review examines the detection of pericyte loss in different diseases, explores the methods employed to assess pericyte coverage, and elucidates the potential mechanisms contributing to pericyte loss in these pathological conditions. Additionally, current therapeutic strategies targeting pericytes are discussed, along with potential future interventions aimed at preserving pericyte function and promoting disease mitigation.
Topics: Humans; Pericytes; Endothelial Cells; Blood-Brain Barrier; Stroke; Brain Injuries, Traumatic
PubMed: 37566011
DOI: 10.3390/cells12151931