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Neural Development Jun 2024Adult neurogenesis, which takes place in both vertebrate and invertebrate species, is the process by which new neurons are born and integrated into existing functional...
Adult neurogenesis, which takes place in both vertebrate and invertebrate species, is the process by which new neurons are born and integrated into existing functional neural circuits, long after embryonic development. Most studies in mammals suggest that self-renewing stem cells are the source of the new neurons, although the extent of self-renewal is a matter of debate. In contrast, research in the crayfish Procambarus clarkii has demonstrated that the neural progenitors producing adult-born neurons are capable of both self-renewing and consuming (non-self-renewing) divisions. However, self-renewing divisions are relatively rare, and therefore the production of adult-born neurons depends heavily on progenitors that are not replenishing themselves. Because the small pool of neural progenitors in the neurogenic niche is never exhausted throughout the long lives of these animals, we hypothesized that there must also be an extrinsic source of these cells. It was subsequently demonstrated that the neural progenitors originate in hemocytes (blood cells) produced by the immune system that travel in the circulation before ultimately integrating into niches where the neural lineage begins. The current study examines the developmental lineage of the three hemocyte types - hyaline (HC), semigranular (SGC) and granular (GC) cells - with the goal of understanding the origins of the progenitor cells that produce adult-born neurons. Longstanding qualitative metrics for hemocyte classification were validated quantitatively. Then, in a longitudinal study, proliferation markers were used to label the hemocytes in vivo, followed by sampling the circulating hemocyte population over the course of two months. Hemolymph samples were taken at intervals to track the frequencies of the different hemocyte types. These data reveal sequential peaks in the relative frequencies of HCs, SGCs and GCs, which were identified using qualitative and quantitative measures. These findings suggest that the three hemocyte types comprise a single cellular lineage that occurs in the circulation, with each type as a sequential progressive stage in hemocyte maturation beginning with HCs and ending with GCs. When combined with previously published data, this timeline provides additional evidence that HCs serve as the primary neural progenitor during adult neurogenesis in P. clarkii.
Topics: Animals; Neurogenesis; Neural Stem Cells; Hemocytes; Cell Lineage; Astacoidea; Neurons
PubMed: 38902780
DOI: 10.1186/s13064-024-00185-3 -
Nature Communications Jun 2024Vertebrates use the phosphate mineral apatite in their skeletons, which allowed them to develop tissues such as enamel, characterized by an outstanding combination of...
Vertebrates use the phosphate mineral apatite in their skeletons, which allowed them to develop tissues such as enamel, characterized by an outstanding combination of hardness and elasticity. It has been hypothesized that the evolution of the earliest vertebrate skeletal tissues, found in the teeth of the extinct group of conodonts, was driven by adaptation to dental function. We test this hypothesis quantitatively and demonstrate that the crystallographic order increased throughout the early evolution of conodont teeth in parallel with morphological adaptation to food processing. With the c-axes of apatite crystals oriented perpendicular to the functional feeding surfaces, the strongest resistance to uniaxial compressional stress is conferred along the long axes of denticles. Our results support increasing control over biomineralization in the first skeletonized vertebrates and allow us to test models of functional morphology and material properties across conodont dental diversity.
Topics: Biomineralization; Animals; Tooth; Biological Evolution; Fossils; Apatites; Dental Enamel; Vertebrates
PubMed: 38902270
DOI: 10.1038/s41467-024-49526-0 -
Environmental Health Perspectives Jun 2024Cadmium (Cd) is a highly toxic and widespread environmental oxidative stressor that causes a myriad of health problems, including osteoporosis and bone damage. Although...
BACKGROUND
Cadmium (Cd) is a highly toxic and widespread environmental oxidative stressor that causes a myriad of health problems, including osteoporosis and bone damage. Although nuclear factor erythroid 2-related factor 2 (NRF2) and its Cap 'n' Collar and basic region Leucine Zipper (CNC-bZIP) family member nuclear factor erythroid 2-related factor 1 (NRF1) coordinate various stress responses by regulating the transcription of a variety of antioxidant and cytoprotective genes, they play distinct roles in bone metabolism and remodeling. However, the precise roles of both transcription factors in bone loss induced by prolonged Cd exposure remain unclear.
OBJECTIVES
We aimed to understand the molecular mechanisms underlying Cd-induced bone loss, focusing mainly on the roles of NRF2 and NRF1 in osteoclastogenesis provoked by Cd.
METHODS
Male wild-type (WT), global -knockout () and myeloid-specific knockout [(M)-KO] mice were administered Cd (50 or ) via drinking water for 8 or 16 wk, followed by micro-computed tomography, histological analyses, and plasma biochemical testing. Osteoclastogenesis was evaluated using bone marrow-derived osteoclast progenitor cells (BM-OPCs) and RAW 264.7 cells in the presence of Cd (10 or ) with a combination of genetic and chemical modulations targeting NRF2 and NRF1.
RESULTS
Compared with relevant control mice, global or (M)-KO mice showed exacerbated bone loss and augmented osteoclast activity following exposure to Cd in drinking water for up to 16 wk. osteoclastogenic analyses suggested that -deficient BM-OPCs and RAW 264.7 cells responded more robustly to low levels of Cd (up to ) with regard to osteoclast differentiation compared with WT cells. Further mechanistic studies supported a compensatory up-regulation of long isoform of NRF1 (L-NRF1) and subsequent induction of nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 1 (NFATc1) as the key molecular events in the deficiency-worsened and Cd-provoked osteoclastogenesis. L- silenced (via lentiviral means) -knockdown (KD) RAW cells exposed to Cd showed dramatically different NFATc1 and subsequent osteoclastogenesis outcomes compared with the cells of -KD alone exposed to Cd, suggesting a mitigating effect of the silencing. In addition, suppression of reactive oxygen species by exogenous antioxidants -acetyl-l-cysteine () and mitoquinone mesylate (MitoQ; ) mitigated the L-NRF1-associated effects on NFATc1-driven osteoclastogenesis outcomes in Cd-exposed -KD cells.
CONCLUSIONS
This and study supported the authors' hypothesis that Cd exposure caused bone loss, in which NRF2 and L-NRF1 responded to Cd and osteoclastogenic stimuli in a cooperative, but contradictive, manner to coordinate expression, osteoclastogenesis and thus bone homeostasis. Our study suggests a novel strategy targeting NRF2 and L-NRF1 to prevent and treat the bone toxicity of Cd. https://doi.org/10.1289/EHP13849.
Topics: Animals; Mice; Male; Cadmium; NF-E2-Related Factor 2; Osteoclasts; Osteogenesis; Mice, Knockout; NF-E2-Related Factor 1; Mice, Inbred C57BL; Cell Differentiation
PubMed: 38896780
DOI: 10.1289/EHP13849 -
Nutrients Jun 2024The placenta is the largest fetal organ, which connects the mother to the fetus and supports most aspects of organogenesis through the transport of nutrients and gases.... (Review)
Review
Association of Placental Pathology with Physical and Neuronal Development of Infants: A Narrative Review and Reclassification of the Literature by the Consensus Statement of the Amsterdam Placental Workshop Group.
The placenta is the largest fetal organ, which connects the mother to the fetus and supports most aspects of organogenesis through the transport of nutrients and gases. However, further studies are needed to assess placental pathology as a reliable predictor of long-term physical growth or neural development in newborns. The Consensus Statement of the Amsterdam Placental Workshop Group (APWGCS) on the sampling and definition of placental lesions has resulted in diagnostic uniformity in describing the most common pathological lesions of the placenta and contributed to the international standardization of descriptions of placental pathology. In this narrative review, we reclassified descriptions of placental pathology from previously published papers according to the APWGCS criteria and comparatively assessed the relationship with infantile physical and/or neural development. After reclassification and reevaluation, placental pathology of maternal vascular malperfusion, one of the APWGCS criteria, emerged as a promising candidate as a universal predictor of negative infantile neurodevelopmental outcomes, not only in term and preterm deliveries but also in high-risk groups of very low birthweight newborns. However, there are few studies that examined placental pathology according to the full categories of APWGCS and also included low-risk general infants. It is necessary to incorporate the assessment of placental pathology utilizing APWGCS in the design of future birth cohort studies as well as in follow-up investigations of high-risk infants.
Topics: Humans; Pregnancy; Female; Placenta; Infant, Newborn; Consensus; Placenta Diseases; Child Development; Infant; Netherlands
PubMed: 38892717
DOI: 10.3390/nu16111786 -
International Journal of Molecular... Jun 2024Regenerative medicine aims to address substantial defects by amplifying the body's natural regenerative abilities and preserving the health of tissues and organs. To... (Review)
Review
Regenerative medicine aims to address substantial defects by amplifying the body's natural regenerative abilities and preserving the health of tissues and organs. To achieve these goals, materials that can provide the spatial and biological support for cell proliferation and differentiation, as well as the micro-environment essential for the intended tissue, are needed. Scaffolds such as polymers and metallic materials provide three-dimensional structures for cells to attach to and grow in defects. These materials have limitations in terms of mechanical properties or biocompatibility. In contrast, biominerals are formed by living organisms through biomineralization, which also includes minerals created by replicating this process. Incorporating biominerals into conventional materials allows for enhanced strength, durability, and biocompatibility. Specifically, biominerals can improve the bond between the implant and tissue by mimicking the micro-environment. This enhances cell differentiation and tissue regeneration. Furthermore, biomineral composites have wound healing and antimicrobial properties, which can aid in wound repair. Additionally, biominerals can be engineered as drug carriers, which can efficiently deliver drugs to their intended targets, minimizing side effects and increasing therapeutic efficacy. This article examines the role of biominerals and their composite materials in regenerative medicine applications and discusses their properties, synthesis methods, and potential uses.
Topics: Regenerative Medicine; Humans; Biocompatible Materials; Animals; Tissue Scaffolds; Tissue Engineering; Minerals; Biomineralization; Wound Healing; Cell Differentiation
PubMed: 38892335
DOI: 10.3390/ijms25116147 -
International Journal of Molecular... May 2024Skeletal muscle grows in response to a combination of genetic and environmental factors, and its growth and development influence the quality of pork. Elucidating the...
Skeletal muscle grows in response to a combination of genetic and environmental factors, and its growth and development influence the quality of pork. Elucidating the molecular mechanisms regulating the growth and development of skeletal muscle is of great significance to both animal husbandry and farm management. The is an excellent pig breed based on the original , importing the genes of the for meat traits, and cultivated through years of scientific selection and breeding. In this study, full-length transcriptome sequencing was performed on three growth stages of , aiming to study the developmental changes in at different developmental stages at the molecular level and to screen the key genes affecting the growth of skeletal muscle in . We performed an enrichment analysis of genes showing differential expression and constructed a protein-protein interaction network with the aim of identifying core genes involved in the development of . Notably, genes such as , , , and may be potential regulators of muscle development in . Our results contribute to the understanding of the molecular mechanisms of skeletal muscle development in this pig breed, which will facilitate molecular breeding efforts and the development of pig breeds to meet the needs of the livestock industry.
Topics: Animals; Muscle, Skeletal; Swine; Gene Expression Profiling; Transcriptome; Gene Expression Regulation, Developmental; Muscle Development; Breeding; Protein Interaction Maps
PubMed: 38892283
DOI: 10.3390/ijms25116095 -
International Journal of Molecular... May 2024Jeryak is the F1 generation of the cross between Gannan yak and Jersey cattle, which has the advantages of fast growth and high adaptability. The growth and development...
Jeryak is the F1 generation of the cross between Gannan yak and Jersey cattle, which has the advantages of fast growth and high adaptability. The growth and development of skeletal muscle is closely linked to meat production and the quality of meat. However, the molecular regulatory mechanisms of muscle growth differences between Gannan yak and Jeryak analyzed from the perspective of chromatin opening have not been reported. In this study, ATAC-seq was used to analyze the difference of chromatin openness in longissimus muscle of Gannan yak and Jeryak. It was found that chromatin accessibility was more enriched in Jeryak compared to Gannan yak, especially in the range of the transcription start site (TSS) ± 2 kb. GO and KEGG enrichment analysis indicate that differential peak-associated genes are involved in the negative regulation of muscle adaptation and the Hippo signaling pathway. Integration analysis of ATAC-seq and RNA-seq revealed overlapping genes were significantly enriched during skeletal muscle cell differentiation and muscle organ morphogenesis. At the same time, we screened , , and for possible involvement in skeletal muscle development, constructed a genes and transcription factors network map, and found that some transcription factors (TFs), including YY1, KLF4, KLF5 and Bach1, were involved in skeletal muscle development. Overall, we have gained a comprehensive understanding of the key factors that impact skeletal muscle development in various breeds of cattle, providing new insights for future analysis of the molecular regulatory mechanisms involved in muscle growth and development.
Topics: Animals; Cattle; Muscle, Skeletal; RNA-Seq; Chromatin Immunoprecipitation Sequencing; Muscle Development; Chromatin; Meat; Transcription Factors
PubMed: 38892214
DOI: 10.3390/ijms25116029 -
International Journal of Molecular... May 2024In exploring the challenges of bone repair and regeneration, this review evaluates the potential of bone tissue engineering (BTE) as a viable alternative to traditional... (Review)
Review
In exploring the challenges of bone repair and regeneration, this review evaluates the potential of bone tissue engineering (BTE) as a viable alternative to traditional methods, such as autografts and allografts. Key developments in biomaterials and scaffold fabrication techniques, such as additive manufacturing and cell and bioactive molecule-laden scaffolds, are discussed, along with the integration of bio-responsive scaffolds, which can respond to physical and chemical stimuli. These advancements collectively aim to mimic the natural microenvironment of bone, thereby enhancing osteogenesis and facilitating the formation of new tissue. Through a comprehensive combination of in vitro and in vivo studies, we scrutinize the biocompatibility, osteoinductivity, and osteoconductivity of these engineered scaffolds, as well as their interactions with critical cellular players in bone healing processes. Findings from scaffold fabrication techniques and bio-responsive scaffolds indicate that incorporating nanostructured materials and bioactive compounds is particularly effective in promoting the recruitment and differentiation of osteoprogenitor cells. The therapeutic potential of these advanced biomaterials in clinical settings is widely recognized and the paper advocates continued research into multi-responsive scaffold systems.
Topics: Tissue Engineering; Tissue Scaffolds; Humans; Bone Regeneration; Animals; Bone and Bones; Biocompatible Materials; Osteogenesis; Cell Differentiation
PubMed: 38892199
DOI: 10.3390/ijms25116012 -
International Journal of Molecular... May 2024Toll-like receptors (TLRs) are among the main components of the innate immune system. They can detect conserved structures in microorganisms and molecules associated... (Review)
Review
Toll-like receptors (TLRs) are among the main components of the innate immune system. They can detect conserved structures in microorganisms and molecules associated with stress and cellular damage. TLRs are expressed in resident immune cells and both neurons and glial cells of the nervous system. Increasing evidence is emerging on the participation of TLRs not only in the immune response but also in processes of the nervous system, such as neurogenesis and cognition. Below, we present a review of the literature that evaluates the expression and role of TLRs in processes such as neurodevelopment, behavior, cognition, infection, neuroinflammation, and neurodegeneration.
Topics: Humans; Toll-Like Receptors; Neurogenesis; Animals; Nervous System; Immunity, Innate; Neurons; Neuroinflammatory Diseases; Signal Transduction
PubMed: 38891900
DOI: 10.3390/ijms25115711 -
International Journal of Molecular... May 2024Articular cartilage damage still remains a major problem in orthopedical surgery. The development of tissue engineering techniques such as autologous chondrocyte...
Articular cartilage damage still remains a major problem in orthopedical surgery. The development of tissue engineering techniques such as autologous chondrocyte implantation is a promising way to improve clinical outcomes. On the other hand, the clinical application of autologous chondrocytes has considerable limitations. Mesenchymal stromal cells (MSCs) from various tissues have been shown to possess chondrogenic differentiation potential, although to different degrees. In the present study, we assessed the alterations in chondrogenesis-related gene transcription rates and extracellular matrix deposition levels before and after the chondrogenic differentiation of MSCs in a 3D spheroid culture. MSCs were obtained from three different tissues: umbilical cord Wharton's jelly (WJMSC-Wharton's jelly mesenchymal stromal cells), adipose tissue (ATMSC-adipose tissue mesenchymal stromal cells), and the dental pulp of deciduous teeth (SHEDs-stem cells from human exfoliated deciduous teeth). Monolayer MSC cultures served as baseline controls. Newly formed 3D spheroids composed of MSCs previously grown in 2D cultures were precultured for 2 days in growth medium, and then, chondrogenic differentiation was induced by maintaining them in the TGF-β1-containing medium for 21 days. Among the MSC types studied, WJMSCs showed the most similarities with primary chondrocytes in terms of the upregulation of cartilage-specific gene expression. Interestingly, such upregulation occurred to some extent in all 3D spheroids, even prior to the addition of TGF-β1. These results confirm that the potential of Wharton's jelly is on par with adipose tissue as a valuable cell source for cartilage engineering applications as well as for the treatment of osteoarthritis. The 3D spheroid environment on its own acts as a trigger for the chondrogenic differentiation of MSCs.
Topics: Mesenchymal Stem Cells; Humans; Chondrogenesis; Cell Differentiation; Extracellular Matrix; Spheroids, Cellular; Chondrocytes; Cells, Cultured; Wharton Jelly; Adipose Tissue; Cell Culture Techniques; Tissue Engineering; Cartilage; Tooth, Deciduous; Dental Pulp
PubMed: 38891883
DOI: 10.3390/ijms25115695