Search Results (67)

Distant hybridization is key to trait innovation and speciation, with Cyprinidae hybrid phylogeny helping to clarify diversification mechanisms. Yet, a major gap persists in Cyprinidae studies: the stabilization mechanisms of interspecific distant hybrid lineages. To address this, we systematically analyzed the molecular phylogeny of seven Cyprinidae distant hybrid lineages and their parental species, using an integrative genetic framework encompassing four mitochondrial genes (Cytb, COI, 16S rRNA, D-loop) and five nuclear genes (EGR2b, IRBP2, RAG1, RAG2, RH2). Homologous sequences of 41 representative Cyprinidae species (85 samples) were retrieved from GenBank to supplement the dataset. Phylogenies were reconstructed from concatenated sequences, complemented by haplotype networks. Intra-/interspecific divergence was quantified using two mitochondrial genes (COI, Cytb) and two nuclear (RAG1, RH2). The results showed that these hybrid lineages exhibited variation patterns analogous to other Cyprinidae species. Both ML and BI trees reconstructed exhibited congruent topologies with high support (bootstrap/BPP > 80%), resolving genus/species-level relationships. While most hybrids clustered intermediately between their parental species, they typically displayed maternal affinity. A notable exception was the 2nNCRC (a homodiploid hybrid from Cyprinus carpio ♀ × Megalobrama amblycephala ♂), which displayed convergent evolution toward Carassius auratus. COI-based K2P genetic distance analysis revealed 2nNCRC had a much closer relationship with C. auratus (0.0119) than with its parents (0.1249 to C. carpio, 0.1552 to M. amblycephala). These nine genes elucidate the genetic relationships between Cyprinid hybrid lineages and progenitors, serving as pivotal molecular markers for parentage tracing and genetic dissection of distant hybridization mechanisms. The integrated mitochondrial–nuclear marker system in this study advances understanding of cytonuclear coadaptation and the stabilization of interspecific distant hybrid lineages in Cyprinidae. Specifically, it provides a precise tool for parentage tracing, Cyprinid germplasm conservation, and targeted regulation of hybrid breeding—laying a foundation for exploring hybrid speciation and developing elite aquaculture germplasms. Full article

Rafiq syndrome (RAFQS) is a rare autosomal recessive disorder that is classified as a type II congenital disorder of glycosylation (CDG-II), and caused by MAN1B1 gene mutation. To date, 24 pathogenic MAN1B1 mutations have been reported in association with MAN1B1-CDG. However, the underlying pathogenic mechanisms remain poorly understood. In this study, we recruited a consanguineous family from Pakistan with multiple affected individuals exhibiting mild facial dysmorphism, developmental delay, and intellectual disability. Utilizing exome sequencing and homozygosity mapping, we identified a novel MAN1B1 mutation (c.772_775del) that co-segregated with RAFQS in this family. Analysis of public single-cell transcriptomic data revealed that MAN1B1 is predominantly expressed in dorsal progenitors and intermediate excitatory neurons during human brain development. Knockdown of Man1b1 in primarily cultured mouse excitatory neurons disrupted axon growth, dendrite formation, and spine maturation, and could not be rescued by truncated variants identified in the family. Furthermore, in utero, electroporation experiments revealed that Man1b1 knockdown in the murine cortex impaired neural stem cells’ proliferation and differentiation, as well as cortical neuron migration. Collectively, these findings elucidate a critical role for MAN1B1 in the etiology of RAFQS and demonstrate that loss-of-function mutation in MAN1B1 disrupt neuro-developmental processes, providing mechanistic insights into the pathogenesis of this disorder. Full article

The mammalian amygdala is located in the temporal lobe of the telencephalon and plays a key role in limbic processing. Recently, our group proposed a radial morphological model to understand the glutamatergic (pallial) part of this nuclear complex in terms of separate progenitor domains. This model explains the amygdala region as consisting of several adjacent developmental radial progenitor units, disposing their distinct periventricular, intermediate, and superficial strata from the ventricle to the pial surface. It was expected that cell populations belonging to specific progenitor domains would present greater molecular similarity to each other than to neighboring developmental units. In this work, we aim to corroborate the existence of several radial domains in the pallial amygdala at the transcriptomic level. snRNAseq experiments in the amygdala of adult mice of both sexes indicated that at low resolution, the whole pallial amygdala was found to divide into two super-radial domains distinguished by differential expression of Slc17a6 and Slc17a7; the former partly imitates molecularly the subpallial (output) amygdalar regions, whereas the rest of the pallial amygdala is molecularly more akin to the surrounding cortical areas. In addition, our snRNAseq transcriptomic analysis fully supports the postulated amygdalar radial model of four main radial domains. Full article

Modern wheat breeding has largely emphasized aboveground traits, often at the expense of belowground characteristics such as root biomass, architecture, and beneficial microbial associations. This has narrowed genetic diversity, impacting traits essential for stress resilience and efficient nutrient and water acquisition—factors expected to become increasingly critical under climate change. In this study, we evaluated 36 primary synthetic (PS) hexaploid wheat lines developed by crossing Aegilops tauschii with the durum wheat cultivar Langdon (LNG) and compared them with LNG and the hexaploid variety Norin 61 (N61). We observed significant variation in root length, biomass, and associations with fungal endophytes, including beneficial Arbuscular Mycorrhizal Fungi (AMF) and Serendipita indica, and pathogenic Alternaria sp. Clustering analysis based on these traits identified three distinct PS groups: (1) lines with greater root length and biomass, high AMF and S. indica colonization, and low Alternaria infection; (2) lines with intermediate traits; and (3) lines with reduced root traits and high Alternaria susceptibility. Notably, these phenotypic patterns corresponded closely with the soil classification of the Ae. tauschii progenitors’ origin, such as Cambisols (supportive of root growth), and Gleysols and Calcisols (restrictive of root growth). This highlights the soil microenvironment as a key determinant of belowground trait expression. By comparing PS lines with domesticated tetraploid and hexaploid wheat, we identified and selected PS lines derived from diverse Ae. tauschii with enhanced root traits. Our study emphasizes the potential of wild D-genome diversity to restore critical root traits for breeding resilient wheat. Full article

In a susceptible individual, persistent, low-level injury to the airway epithelium initiates an exaggerated wound repair response, ultimately leading to idiopathic pulmonary fibrosis (IPF). The mechanisms driving this fibroproliferative response are not fully understood. Here, we review recent spatially resolved transcriptomics and proteomics studies that provide insight into two distinct matricellular microenvironments important in this pathological fibroproliferation. First, in response to alveolar epithelial injury, alveolar differentiation intermediate (ADI) basal cells arising from Secretoglobin (Scgb1a1) progenitors re-populate the injured alveolus remodeling the extracellular matrix (ECM). ADI cells exhibit an interconnected cellular stress response involving the unfolded protein response (UPR), epithelial–mesenchymal transition (EMT) and senescence pathways. These pathways reprogram cellular metabolism to support fibrillogenic ECM remodeling. In turn, the remodeled ECM tonically stimulates EMT in the ADI population, perpetuating the transitional cell state. Second, fibroblastic foci (FF) are a distinct microenvironment composed of activated aberrant “basaloid” cells supporting transition of adjacent mesenchyme into hyaluronan synthase (HAS^hi)-expressing fibroblasts and myofibroblasts. Once formed, FF are the major matrix-producing factories that invade and disrupt the alveolar airspace, forming a mature scar. In both microenvironments, the composition and characteristics of the ECM drive persistence of atypical epithelium sustaining matrix production. New approaches to monitor cellular trans-differentiation and matrix characteristics using positron emission tomography (PET)–magnetic resonance imaging (MRI) and optical imaging are described, which hold the potential to monitor the effects of therapeutic interventions to modify the ECM. Greater understanding of the bidirectional interrelationships between matrix and cellular phenotypes will identify new therapeutics and diagnostics to affect the outcomes of this lethal disease. Full article

Background: GABAergic signaling plays a crucial role in modulating neuronal proliferation, migration, and the formation of neural network connections. The termination of GABA transmission primarily occurs through the action of GABA transporter 1 (GAT1), encoded by the SLC6A1 gene. Multiple SLC6A1 mutations have been implicated in neurodevelopmental disorders, but their effects on the nervous system are unclear. Methods: We estimated the expression pattern of the GAT1 (S295L) protein using the Slc6a1^S295L/S295L mouse model via RT-PCR, Western blotting, and confocal immunofluorescence. The effect of GAT1 (S295L) on hippocampal neurogenesis was investigated by neuronal marker staining (Sox2, Tbr2, NeuroD1, DCX, NeuN) and BrdU label experiments. The dendritic complexity was mapped through Sholl analysis. RNA-Seq was utilized to explore the signaling pathways and molecules associated with neurodevelopmental disorders. Results: We detected a remarkable decline in the quantity of type-2b intermediate progenitor cells, neuroblasts, and immature neurons in the dentate gyrus (DG) of Slc6a1^S295L/S295L mice at 4 weeks. These abnormalities were exacerbated in adulthood, as evidenced by compromised dendritic length and height as well as the complexity of immature neurons. Immunofluorescence staining showed the abnormal aggregation of GAT1 (S295L) protein in neurons. RNA-seq analysis identified pathways associated with neurodevelopment, neurological disorders, protein homeostasis, and neuronutrition. The neurotrophin Bdnf decreased at all ages in the Slc6a1^S295L/S295L mice. Conclusions: Our data provide new evidence that GAT1 (S295L) causes impaired neurogenesis in the DG. GAT1 mutation not only disrupts GABA homeostasis but also impairs the neurotrophic support necessary for normal hippocampal development, which may be one of the factors contributing to impaired neurogenesis. Full article

Background: The intermediate filament nestin was first described in stem and progenitor cells of neural and mesenchymal origin. Additionally, it is expressed in endothelial cells during wound healing and tumorigenesis. Thus, nestin is widely regarded as a marker for proliferative endothelium. However, little is known about its role in lymphatic endothelium. Methods: Here, we analyzed the expression of nestin in the endothelium of ten human haemangiomas and ten lymphangiomas in situ by immunohistochemistry. This study aimed to investigate the expression of nestin in haemangiomas and lymphangiomas to determine its potential role as a vascular marker. Specifically, we aimed to assess whether nestin expression is restricted to proliferating endothelial cells or also present in non-proliferative blood vessels. Results: Immunohistochemically, haemangiomas were positive for CD31 but negative for D2-40. The endothelial cells within these lesions showed a homogeneous expression of nestin. In contrast, the endothelium of lymphangiomas reacted positively for D2-40 and CD31 but did not show any nestin expression. Additionally, only a few endothelial cells of capillary haemangiomas showed a Ki-67 positivity. Conclusions: The differential expression of nestin in haemangiomas and lymphangiomas indicates a specificity of nestin for the endothelium of blood vessels. The Ki-67 negativity in the majority of the endothelial cells reveals the proliferative quiescence of these cells. These findings indicate that nestin could be used as a marker to differentiate between blood and lymphatic vessels. Full article

Neural progenitor cells (NPCs) are often used to study the subcellular mechanisms underlying differentiation into neurons in vitro. Works published to date have focused on the pathways that distinguish undifferentiated NPCs from mature neurons, neglecting the earlier and intermediate stages of this process. Current evidence suggests that mitochondria interaction with the ER is fundamental to a wide range of intracellular processes. However, it is not clear whether and how the mitochondria–ER interactions differ between NPCs and their differentiated counterparts. Here we take advantage of the widely used NPC line LUHMES to provide hints on the mitochondrial dynamic trait changes that occur during the first stage of their maturation into dopaminergic-like neurons. We observed that the morphology of mitochondria, their interaction with the ER, and the expression of several mitochondria–ER contact site resident proteins change, which suggests the potential contribution of mitochondria dynamics to NPC differentiation. Further studies will be needed to explore in depth these changes, and their functional outcomes, which may be relevant to the scientific community focusing on embryonic neurogenesis and developmental neurotoxicity. Full article

The genome composition of intermediate wheatgrass (IWG; Thinopyrum intermedium (Host) Barkworth and D.R. Dewey; 2n = 6x = 42) is complex and remains to be a subject of ongoing investigation. This study employed fluorescence in situ hybridization (FISH) to analyze the karyotype of Th. intermedium and its related species. With the St₂-80 probe derived from Pseudoroegneria strigosa and the pDb12H probe from Dasypyrum breviaristatum, FISH analysis classified the chromosomes of Th. intermedium as J^vsJ^vsJ^rJ^rStSt. FISH karyotype was established using pSc119.2-1, (GAA)₁₀, AFA-3, AFA-4, pAs1-1, pAs1-3, pAs1-4, and pAs1-6 as a combined multiplex oligonucleotide probe. MATO software was used to analyze chromosome length, arm ratio, and karyotype structure. The karyotype formula of Th. intermedium is K(2n) = 6X = 42 = 36m + 6sm, and that of Th. junceiforme is K(2n) = 4X = 28 = 22m + 6sm. The karyotype formula of Th. elongatum and Th. bessarabicum is K(2n) = 2X = 14 = 12m + 2sm, of Ps. spicata is K(2n) = 2X = 14 = 2M + 12m, and of Da. villosum is K(2n) = 2X = 14 = 12m + 2sm. Based on the results of FISH, standard karyotypes of Th. intermedium and its potential progenitor species were constructed. These standard karyotypes revealed that there was evolutionary parallelism between genome and karyotype, but due to the complexity of evolution, the FISH signal of Th. intermedium was abundant and asymmetrical. Full article

Planetary nebulae (PNe) are the ejected gas and dust shells of evolved low- and intermediate-mass stars (LIMSs). We present an abundance comparison between PNe and their progenitors to reveal their similarities and differences since such a comparison has rarely, and not recently, been performed in the Milky Way. The dynamical expulsion of the outer envelope of an evolved LIMS produces the PN. We expected similarities in most $\alpha$-element distributions across the stellar and nebular populations, given that these elements are only marginally produced and destroyed during the LIMS evolution. Differences found in the Fe and S abundances allow us to determine their depletion due to grain condensation in the post-AGB phases. Differences in N and C between PNe and their progenitors set new limits to the low- and intermediate-mass star contributions to these elements. Finally, radial metallicity gradients from evolved LIMS and PNe and Gaia-calibrated distances constrain Galactic evolution in the framework of the current chemical evolutionary models. We found the following: (1) Gas-phase iron is significantly depleted in PNe compared to their progenitor stars, with an average depletion factor of <D[Fe/H]> = 1.74 ± 0.49. (2) Sulfur is also depleted in PNe, though to a much lesser extent than iron. (3) The median enrichment levels for carbon and nitrogen relative to the median stellar population of the same metallicity are approximately [C/H] ∼ +0.3 and [N/H] ∼ +0.4, respectively. PNe with progenitors that experienced hot-bottom burning (HBB) exhibit extreme nitrogen enrichment. (4) With the data available to date, the radial metallicity gradient derived from evolved LIMSs and PNe are compatible within the uncertainties. Full article

DNA methylation and demethylation are key epigenetic events that regulate gene expression and cell fate. DNA demethylation via oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) is typically mediated by TET (ten-eleven translocation) enzymes. The 5hmC modification is considered an intermediate state of DNA demethylation; it is particularly prevalent in the brain and is believed to play a role in the development of many cell types in the brain. Our previous studies have identified that vitamin C (Vc) and MEK inhibitor PD0325901 could significantly promote OPC (oligodendrocyte progenitor cell)-to-OL (oligodendrocyte) differentiation. Here we discovered that Vc and PD0325901 may promote OPC-to-OL differentiation by inducing DNA demethylation via hydroxymethylation. Blocking 5hmC formation almost totally blocked Vc- and PD0325901-stimulated OPC-to-OL differentiation. In addition, TET1 is not involved in Vc,- and PD0325901-promoted OL generation. We also found a synergistic effect between the two compounds in inducing OL generation, suggesting the possibility of a combination therapy for demyelination diseases in the future. Full article

The asymptotic giant branch (AGB) phase, experienced by low- and intermediate-mass stars (LIMSs), plays a crucial role in galaxies due to its significant dust production. Planetary nebulae (PNe) offer a novel perspective, providing valuable insights into the dust production mechanisms and the evolutionary history of LIMSs. We selected a sample of nine PNe from the Large Magellanic Cloud (LMC), likely originating from single stars. By modeling their spectral energy distributions (SEDs) with photoionization techniques, we successfully reproduced the observed photometric data, spectra, and chemical abundances. This approach enabled us to constrain key characteristics of the central stars (CSs), dust, and gaseous nebulae, which were then compared with predictions from stellar evolution models. By integrating observational data across ultraviolet (UV) to infrared (IR) wavelengths, we achieved a comprehensive understanding of the structure of the PNe in our sample. The results of the SED analysis are consistent with evolutionary models and previous studies that focus on individual components of the PN, such as dust or the gaseous nebula. Our analysis enabled us to determine the metallicity, the progenitor mass of the CSs, and the amount of dust and gas surrounding the CSs, linking these properties to the previous AGB phase. The PN phase provides critical insights into the physical processes active during earlier evolutionary stages. Additionally, we found that higher progenitor masses are associated with greater amounts of dust in the surrounding nebulae but lower amounts of gaseous material compared to sources with lower progenitor masses. Full article

Platelets are the terminal progeny of megakaryocytes, primarily produced in the bone marrow, and play critical roles in blood homeostasis, clotting, and wound healing. Traditionally, megakaryocytes and platelets are thought to arise from multipotent hematopoietic stem cells (HSCs) via multiple discrete progenitor populations with successive, lineage-restricting differentiation steps. However, this view has recently been challenged by studies suggesting that (1) some HSC clones are biased and/or restricted to the platelet lineage, (2) not all platelet generation follows the “canonical” megakaryocytic differentiation path of hematopoiesis, and (3) platelet output is the default program of steady-state hematopoiesis. Here, we specifically investigate the evidence that in vivo lineage tracing studies provide for the route(s) of platelet generation and investigate the involvement of various intermediate progenitor cell populations. We further identify the challenges that need to be overcome that are required to determine the presence, role, and kinetics of these possible alternate pathways. Full article

Neuromesodermal progenitors (NMPs), serving as the common origin of neural and paraxial mesodermal development in a large part of the trunk, have recently gained significant attention because of their critical importance in the understanding of embryonic organogenesis and the design of in vitro models of organogenesis. However, the nature of NMPs at many essential points remains only vaguely understood or even incorrectly assumed. Here, we discuss the nature of NMPs, focusing on their dynamic migratory behavior during embryogenesis and the mechanisms underlying their neural vs. mesodermal fate choice. The discussion points include the following: (1) How the sinus rhomboidals is organized; the tissue where the neural or mesodermal fate choice of NMPs occurs. (2) NMPs originating from the broad posterior epiblast are associated with Sox2 N1 enhancer activity. (3) Tbx6-dependent Sox2 repression occurs during NMP-derived paraxial mesoderm development. (4) The nephric mesenchyme, a component of the intermediate mesoderm, was newly identified as an NMP derivative. (5) The transition of embryonic tissue development from tissue-specific progenitors in the anterior part to that from NMPs occurs at the forelimb bud axial level. (6) The coexpression of Sox2 and Bra in NMPs is conditional and is not a hallmark of NMPs. (7) The ability of the NMP pool to sustain axial embryo growth depends on Wnt3a signaling in the NMP population. Current in vitro models of NMPs are also critically reviewed. Full article

Congenital Zika syndrome (CZS) is a set of birth defects caused by Zika virus (ZIKV) infection during pregnancy. Microcephaly is its main feature, but other brain abnormalities are found in CZS patients, such as ventriculomegaly, brain calcifications, and dysgenesis of the corpus callosum. Many studies have focused on microcephaly, but it remains unknown how ZIKV infection leads to callosal malformation. To tackle this issue, we infected mouse embryos in utero with a Brazilian ZIKV isolate and found that they were born with a reduction in callosal area and density of callosal neurons. ZIKV infection also causes a density reduction in PH3+ cells, intermediate progenitor cells, and SATB2+ neurons. Moreover, axonal tracing revealed that callosal axons are reduced and misrouted. Also, ZIKV-infected cultures show a reduction in callosal axon length. GFAP labeling showed that an in utero infection compromises glial cells responsible for midline axon guidance. In sum, we showed that ZIKV infection impairs critical steps of corpus callosum formation by disrupting not only neurogenesis, but also axon guidance and growth across the midline. Full article