Ependymal cell lineage reprogramming as a potential therapeutic intervention for hydrocephalus.

Hydrocephalus is a common neurological condition, characterized by the excessive accumulation of cerebrospinal fluid in the cerebral ventricles. Primary treatments for hydrocephalus mainly involve neurosurgical cerebrospinal fluid diversion, which hold high morbidity and failure rates, highlighting the necessity for the discovery of novel therapeutic approaches. Although the pathophysiology of hydrocephalus is highly multifactorial, impaired function of the brain ependymal cells plays a fundamental role in hydrocephalus.

GPRC5C drives branched-chain amino acid metabolism in leukemogenesis.

Leukemia stem cells (LSCs) share numerous features with healthy hematopoietic stem cells (HSCs). G-protein coupled receptor family C group 5 member C (GPRC5C) is a regulator of HSC dormancy. However, GPRC5C functionality in acute myeloid leukemia (AML) is yet to be determined.

The long noncoding RNA scaffolds neuronal granules to maintain nervous system maturity.

RNA binding proteins and messenger RNAs (mRNAs) assemble into ribonucleoprotein granules that regulate mRNA trafficking, local translation, and turnover. The dysregulation of RNA-protein condensation disturbs synaptic plasticity and neuron survival and has been widely associated with human neurological disease. Neuronal granules are thought to condense around particular proteins that dictate the identity and composition of each granule type.

Hyaluronic acid-GPRC5C signalling promotes dormancy in haematopoietic stem cells.

Bone marrow haematopoietic stem cells (HSCs) are vital for lifelong maintenance of healthy haematopoiesis. In inbred mice housed in gnotobiotic facilities, the top of the haematopoietic hierarchy is occupied by dormant HSCs, which reversibly exit quiescence during stress. Whether HSC dormancy exists in humans remains debatable.

Avoid shocking your hematopoietic stem cells to keep them young and growing.

Expanding hematopoietic stem cells (HSCs) ex vivo has historically been a very challenging process. In this issue of Cell Stem Cell, Kruta et al. (2021) identify heat shock factor 1 (Hsf1) as a new target to maintain HSC fitness and protein homeostasis, not only in culture conditions but also upon aging.

Multilayer omics analysis reveals a non-classical retinoic acid signaling axis that regulates hematopoietic stem cell identity.

Hematopoietic stem cells (HSCs) rely on complex regulatory networks to preserve stemness. Due to the scarcity of HSCs, technical challenges have limited our insights into the interplay between metabolites, transcription, and the epigenome. In this study, we generated low-input metabolomics, transcriptomics, chromatin accessibility, and chromatin immunoprecipitation data, revealing distinct metabolic hubs that are enriched in HSCs and their downstream multipotent progenitors.

Revisiting the non-Gaucher-GBA-E326K carrier state: Is it sufficient to increase Parkinson's disease risk?

Background: GBA variants are the most common genetic risk factors for Parkinson's disease (PD) world-wide, and can be found in up to 20% of Ashkenazi PD patients. The E326K variant, which is not considered a Gaucher's disease causing mutation, was recently shown to increase the risk for PD. Since E326K is a common variant among Europeans, Finnish and Ashkenazi (2.

GemC1 is a critical switch for neural stem cell generation in the postnatal brain.

The subventricular zone (SVZ) is one of two main niches where neurogenesis persists during adulthood, as it retains neural stem cells (NSCs) with self-renewal capacity and multi-lineage potency. Another critical cellular component of the niche is the population of postmitotic multiciliated ependymal cells. Both cell types are derived from radial glial cells that become specified to each lineage during embryogenesis.

B cell depletion treatment decreases CD4+IL4+ and CD4+CD40L+ T cells in patients with systemic sclerosis.

Recent data suggests that rituximab may favorably affect skin fibrosis and lung function in patients with systemic sclerosis. Based on experimental data suggesting a key role of B and T cells in scleroderma we aimed to explore the effect(s) of rituximab treatment on T cell subpopulations. Fifteen patients with scleroderma who received rituximab treatment and six who received standard treatment alone were recruited.

GemC1 governs multiciliogenesis through direct interaction with and transcriptional regulation of p73.

A distinct combination of transcription factors elicits the acquisition of a specific fate and the initiation of a differentiation program. Multiciliated cells (MCCs) are a specialized type of epithelial cells that possess dozens of motile cilia on their apical surface. Defects in cilia function have been associated with ciliopathies that affect many organs, including brain and airway epithelium.

Adult Neural Stem Cells and Multiciliated Ependymal Cells Share a Common Lineage Regulated by the Geminin Family Members.

Adult neural stem cells and multiciliated ependymal cells are glial cells essential for neurological functions. Together, they make up the adult neurogenic niche. Using both high-throughput clonal analysis and single-cell resolution of progenitor division patterns and fate, we show that these two components of the neurogenic niche are lineally related: adult neural stem cells are sister cells to ependymal cells, whereas most ependymal cells arise from the terminal symmetric divisions of the lineage.

Geminin ablation in vivo enhances tumorigenesis through increased genomic instability.

Geminin, a DNA replication licensing inhibitor, ensures faithful DNA replication in vertebrates. Several studies have shown that geminin depletion in vitro results in rereplication and DNA damage, whereas increased expression of geminin has been observed in human cancers. However, conditional inactivation of geminin during embryogenesis has not revealed any detectable DNA replication defects.

Geminin Participates in Differentiation Decisions of Adult Neural Stem Cells Transplanted in the Hemiparkinsonian Mouse Brain.

Neural stem cells have been considered as a source of stem cells that can be used for cell replacement therapies in neurodegenerative diseases, as they can be isolated and expanded in vitro and can be used for autologous grafting. However, due to low percentages of survival and varying patterns of differentiation, strategies that will enhance the efficacy of transplantation are under scrutiny. In this article, we have examined whether alterations in Geminin's expression, a protein that coordinates the balance between self-renewal and differentiation, can improve the properties of stem cells transplanted in 6-OHDA hemiparkinsonian mouse model.

Mcidas and GemC1/Lynkeas specify embryonic radial glial cells.

Ependymal cells are multiciliated cells located in the wall of the lateral ventricles of the adult mammalian brain and are key components of the subependymal zone niche, where adult neural stem cells reside. Through the movement of their motile cilia, ependymal cells control the cerebrospinal fluid flow within the ventricular system from which they receive secreted molecules and morphogens controlling self-renewal and differentiation decisions of adult neural stem cells. Multiciliated ependymal cells become fully differentiated at postnatal stages however they are specified during mid to late embryogenesis from a population of radial glial cells.

GemC1 controls multiciliogenesis in the airway epithelium.

Multiciliated cells are terminally differentiated, post-mitotic cells that form hundreds of motile cilia on their apical surface. Defects in multiciliated cells lead to disease, including mucociliary clearance disorders that result from ciliated cell disfunction in airways. The pathway controlling multiciliogenesis, however, remains poorly characterized.

Embryonic Poly(A)-Binding Protein (EPAB) Is Required for Granulosa Cell EGF Signaling and Cumulus Expansion in Female Mice.

Embryonic poly(A)-binding protein (EPAB) is the predominant poly(A)-binding protein in Xenopus, mouse, and human oocytes and early embryos before zygotic genome activation. EPAB is required for translational activation of maternally stored mRNAs in the oocyte and Epab(-/-) female mice are infertile due to impaired oocyte maturation, cumulus expansion, and ovulation. The aim of this study was to characterize the mechanism of follicular somatic cell dysfunction in Epab(-/-) mice.

Mcidas and GemC1 are key regulators for the generation of multiciliated ependymal cells in the adult neurogenic niche.

Multiciliated cells are abundant in the epithelial surface of different tissues, including cells lining the walls of the lateral ventricles in the brain and the airway epithelium. Their main role is to control fluid flow and defects in their differentiation are implicated in many human disorders, such as hydrocephalus, accompanied by defects in adult neurogenesis and mucociliary disorder in the airway system. Here we show that Mcidas, which is mutated in human mucociliary clearance disorder, and GemC1 (Gmnc or Lynkeas), previously implicated in cell cycle progression, are key regulators of multiciliated ependymal cell generation in the mouse brain.

Cross-Talk Between FSH and Endoplasmic Reticulum Stress: A Mutually Suppressive Relationship.

Suboptimal cellular conditions result in the accumulation of unfolded proteins in the endoplasmic reticulum (ER) and trigger ER stress. In this study, we investigated the effects of follicle stimulating hormone (FSH) on ER stress in granulosa cells (GCs) obtained from 3-week-old female C57BL6 mice 24 or 48 hours after intraperitoneal injection of 5 IU pregnant mare's serum gonadotropin (PMSG), and in primary mouse GCs in culture treated with FSH (10-100 mIU/mL) for 24 or 48 hours. Moreover, mouse GCs in culture were treated with tunicamycin (Tm) or thapsigargin (Tp), which induce ER stress by inhibiting N-glycosylation of ER proteins and ER calcium adenosine triphosphatase, respectively, and their response to FSH was evaluated.

Altered trafficking and stability of polycystins underlie polycystic kidney disease.

The most severe form of autosomal dominant polycystic kidney disease occurs in patients with mutations in the gene (PKD1) encoding polycystin-1 (PC1). PC1 is a complex polytopic membrane protein expressed in cilia that undergoes autoproteolytic cleavage at a G protein-coupled receptor proteolytic site (GPS). A quarter of PKD1 mutations are missense variants, though it is not clear how these mutations promote disease.

mRNA-binding protein TIA-1 reduces cytokine expression in human endometrial stromal cells and is down-regulated in ectopic endometrium.

Background: Cytokines and growth factors play important roles in endometrial function and the pathogenesis of endometriosis. mRNAs encoding cytokines and growth factors undergo rapid turnover; primarily mediated by adenosine- and uridine-rich elements (AREs) located in their 3'-untranslated regions. T-cell intracellular antigen (TIA-1), an mRNA-binding protein, binds to AREs in target transcripts, leading to decreased gene expression.

Follicle-stimulating hormone receptor (FSHR) alternative skipping of exon 2 or 3 affects ovarian response to FSH.

Genes critical for fertility are highly conserved in mammals. Interspecies DNA sequence variation, resulting in amino acid substitutions and post-transcriptional modifications, including alternative splicing, are a result of evolution and speciation. The mammalian follicle-stimulating hormone receptor (FSHR) gene encodes distinct species-specific forms by alternative splicing.

The transcriptome of follicular cells: biological insights and clinical implications for the treatment of infertility.

Background: Oocyte maturation is under strict regulatory control, not only from intrinsic cellular processes, but also extrinsic influences. While the oocyte is directly connected to the surrounding cumulus cells (CCs) via a network of gap junctions facilitating communication and exchange of molecules, it is also influenced by the greater follicular environment. In order to produce an oocyte capable of successfully transmitting the female genetic material and able to support the earliest stages of preimplantation development, cytoplasmic and nuclear maturation must be achieved.

Human embryonic poly(A)-binding protein (EPAB) alternative splicing is differentially regulated in human oocytes and embryos.

Oocyte maturation is associated with suppression of transcriptional activity. Consequently, gene expression during oocyte maturation, fertilization and early embryo development, until zygotic genome activation (ZGA) is primarily regulated by translational activation of maternally derived mRNAs. Embryonic poly(A)-binding protein (EPAB) is the predominant poly(A)-binding protein in Xenopus, mouse and human oocytes and early embryos prior to ZGA.

Characterization of the gonadotropin releasing hormone receptor (GnRHR) expression and activity in the female mouse ovary.

GnRH agonists (GnRHa) are increasingly used for fertility preservation in women undergoing gonadotoxic chemotherapy. However, the protective mechanisms of action for these compounds have not yet been elucidated. In this study, we aimed to determine whether GnRHa have a direct effect on ovarian granulosa cells.