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Topic Review
Polycomb Proteins
Embryonic development is a highly intricate and complex process. Different regulatory mechanisms cooperatively dictate the fate of cells as they progress from pluripotent stem cells to terminally differentiated cell types in tissues. A crucial regulator of these processes is the Polycomb Repressive Complex 2 (PRC2). By catalyzing the mono-, di-, and tri-methylation of lysine residues on histone H3 tails (H3K27me3), PRC2 compacts chromatin by cooperating with Polycomb Repressive Complex 1 (PRC1) and represses transcription of target genes. Proteomic and biochemical studies have revealed two variant complexes of PRC2, namely PRC2.1 which consists of the core proteins (EZH2, SUZ12, EED, and RBBP4/7) interacting with one of the Polycomb-like proteins (MTF2, PHF1, PHF19), and EPOP or PALI1/2, and PRC2.2 which contains JARID2 and AEBP2 proteins. MTF2 and JARID2 have been discovered to have crucial roles in directing and recruiting PRC2 to target genes for repression in embryonic stem cells (ESCs).
  • 1.1K
  • 23 Aug 2022
Topic Review
Alveologenesis
Alveologenesis is the final stage of lung maturation, when an alveolar region is divided into smaller units called alveoli via the process known as secondary septation. Each of the formed septa serves as a new gas exchange surface, and all together, they dramatically increase the respiratory surface area. Alveologenesis is divided into 2 phases: classical and continued. During the classical alveologenesis, the secondary septa are formed and the number of alveoli increases. During the continued alveologenesis, the maturation and thinning of the septa occur and the size of alveoli increases. The disruption of alveologenesis leads to the simplification of the alveoli, as seen in preterm infants diagnosed with bronchopulmonary dysplasia (BPD), a widespread pulmonary disease that is often connected with lifelong respiratory failure.
  • 991
  • 23 Nov 2021
Topic Review
Chromatoid Bodies in the Regulation of Spermatogenesis
The CB is a membrane-less perinuclear organelle present in male germ cells which serve as storehouse for mRNAs transported by RNA binding and transport proteins like GRTH/DDX25. It also serves as a processing center of mRNAs awaiting translation during later stages of spermatogenesis. These CBs are involved in diverse pathways like RNA transport, decay, surveillance and regulate the stability of mRNAs to secure the correct timing of protein expression at different stages of spermiogenesis.
  • 973
  • 11 Mar 2022
Topic Review
Stem Cell Therapy for Infertility
Stem cells are a subtype of cells that remain in undifferentiated form in embryos and in adult tissues and can self-renew and differentiate as and when required. Stem cells in differentiated organs contribute to the restoration of function through organ damage repair. According to their origin, stem cells are classified as embryonic stem cells (ESC), adult stem cells (includes mesenchymal stem cells MSC), induced pluripotent stem cells (iPSC), spermatogonial stem cells (SSCs), and ovarian stem cells. Stem Cells can be applicable for several disorders including infertility both in male and female.
  • 970
  • 22 Jul 2021
Topic Review
Development of SARS-CoV-2 Variants
A novel coronavirus (SARS-CoV-2) emerged towards the end of 2019 that caused a severe respiratory disease in humans called COVID-19. It led to a pandemic with a high rate of morbidity and mortality that is ongoing and threatening humankind. Most of the mutations occurring in SARS-CoV-2 are synonymous or deleterious, but a few of them produce improved viral functions. The first known mutation associated with higher transmissibility, D614G, was detected in early 2020. Since then, the virus has evolved; new mutations have occurred, and many variants have been described. Depending on the genes affected and the location of the mutations, they could provide altered infectivity, transmissibility, or immune escape. To date, mutations that cause variations in the SARS-CoV-2 spike protein have been among the most studied because of the protein’s role in the initial virus–cell contact and because it is the most variable region in the virus genome. Some concerning mutations associated with an impact on viral fitness have been described in the Spike protein, such as D614G, N501Y, E484K, K417N/T, L452R, and P681R, among others. To understand the impact of the infectivity and antigenicity of the virus, the mutation landscape of SARS-CoV-2 has been under constant global scrutiny. The virus variants are defined according to their origin, their genetic profile (some characteristic mutations prevalent in the lineage), and the severity of the disease they produce, which determines the level of concern. If they increase fitness, new variants can outcompete others in the population. The Alpha variant was more transmissible than previous versions and quickly spread globally. The Beta and Gamma variants accumulated mutations that partially escape the immune defenses and affect the effectiveness of vaccines. Nowadays, the Delta variant, identified around March 2021, has spread and displaced the other variants, becoming the most concerning of all lineages that have emerged. The Delta variant has a particular genetic profile, bearing unique mutations, such as T478K in the spike protein and M203R in the nucleocapsid. This entry summarizes the current knowledge of the different mutations that have appeared in SARS-CoV-2, mainly on the spike protein. It analyzes their impact on the protein function and, subsequently, on the level of concern of different variants and their importance in the ongoing pandemic. 
  • 933
  • 28 Dec 2021
Topic Review
Spleen Reparative Regeneration
The spleen is the largest lymphoid unpaired parenchymal organ of the abdominal cavity found in all vertebrates. Spleen is able to regenerate, though not necessarily to the initial volume. The recovery lasts one month and preserves the architecture, albeit with an increase in the relative volume of lymphoid follicles. The renovated tissues, however, exhibit skewed functional profiles; notably, the decreased production of antibodies and the low cytotoxic activity of T cells, consistent with the decline of T-dependent zones and prolonged reduction in T cell numbers. Autotransplantations of splenic material are of particular clinical interest, as the procedure can possibly mitigate the development of post-splenectomy syndrome. Under these conditions, regeneration lasts 1-2 months, depending on the species. The transplants effectively destroy senescent erythrocytes, assist in microbial clearance, and produce antibodies, thus averting sepsis and bacterial pneumonia. Meanwhile, cellular sources of splenic recovery in such models remain obscure, as well as the time required for T and B cell number re-constitution.
  • 905
  • 21 Jun 2022
Topic Review
Embryonic Retina Self-Organization In Vivo
Self-organization is a process that ensures histogenesis of the eye retina. The phenomenon of self-organisation is discussed in the spatiotemporal context and illustrated by key findings during vertebrate retina development in vivo and retinal regeneration in amphibians in situ. Described also are histotypic 3D structures obtained from the disaggregated retinal progenitor cells of birds and retinal 3D organoids derived from the mouse and human pluripotent stem cells.
  • 902
  • 30 Jun 2022
Topic Review
The “3Ds” of Growing Kidney Organoids
A kidney organoid is a three-dimensional (3D) cellular aggregate grown from stem cells in vitro that undergoes self-organization, recapitulating aspects of normal renal development to produce nephron structures that resemble the native kidney organ. These miniature kidney-like structures can also be derived from primary patient cells and thus provide simplified context to observe how mutations in kidney-disease-associated genes affect organogenesis and physiological function.
  • 896
  • 17 Feb 2023
Topic Review
Air Pollution Affects Placental DNA Methylation
The Developmental Origins of Health and Disease (DOHaD) concept postulates that in utero exposures influence fetal programming and health in later life. Throughout pregnancy, the placenta plays a central role in fetal programming; it regulates the in utero environment and acts as a gatekeeper for nutrient and waste exchange between the mother and the fetus. Maternal exposure to air pollution, including heavy metals, can reach the placenta, where they alter DNA methylation patterns, leading to changes in placental function and fetal reprogramming. In this entry, we explore the current knowledge on placental DNA methylation changes associated with prenatal air pollution (including heavy metals) exposure and highlight its effects on fetal development and disease susceptibility.
  • 882
  • 15 Nov 2021
Topic Review
Endocytosis and Signaling Regulation
Cellular trafficking through the endosomal–lysosomal system is essential for the transport of cargo proteins, receptors and lipids from the plasma membrane inside the cells and across membranous organelles. By acting as sorting stations, vesicle compartments direct the fate of their content for degradation, recycling to the membrane or transport to the trans-Golgi network. To effectively communicate with their neighbors, cells need to regulate their compartmentation and guide their signaling machineries to cortical membranes underlying these contact sites. Endosomal trafficking is indispensable for the polarized distribution of fate determinants, adaptors and junctional proteins. Conversely, endocytic machineries cooperate with polarity and scaffolding components to internalize receptors and target them to discrete membrane domains. Depending on the cell and tissue context, receptor endocytosis can terminate signaling responses but can also activate them within endosomes that act as signaling platforms. Therefore, cell homeostasis and responses to environmental cues rely on the dynamic cooperation of endosomal–lysosomal machineries with polarity and signaling cues. 
  • 852
  • 07 May 2022
Topic Review
Congenital Lung Malformations
Congenital lung malformations arise during development and include numerous anatomical anomalies of the lung and respiratory tree. They are usually detected prenatally by ultrasonography and comprise congenital pulmonary airway malformation (CPAM), bronchopulmonary sequestration (BPS), bronchogenic cysts (BC), and more rarely bronchial atresia, congenital lobar emphysema (CLE), and congenital tracheal obstruction. This entry focuses on the molecular and genetic determinants of the most frequent anomalies: CPAM, BPS, and BC. Congenital diaphragmatic hernia (CDH) is not usually included in this group; however, since the lung is also highly affected in this condition, we have also incorporated evidence related to lung hypoplasia.
  • 851
  • 30 Nov 2021
Topic Review
Autosomal Dominant Lateral Temporal Epilepsy
Autosomal dominant lateral temporal epilepsy (ADLTE) is a genetic focal epilepsy associated with mutations in the LGI1, RELN, and MICAL1 genes. A previous study linking ADLTE with two MICAL1 mutations that resulted in the substitution of a highly conserved glycine residue for serine (G150S) or a frameshift mutation that swapped the last three C-terminal amino acids for 59 extra residues (A1065fs) concluded that the mutations increased enzymatic activity and promoted cell contraction.
  • 824
  • 11 May 2022
Topic Review
Ubiquitination of ETS Transcription Factors
Genome expansion, whole genome and gene duplication events during metazoan evolution produced an extensive family of ETS genes whose members express transcription factors with a conserved winged helix-turn-helix DNA-binding domain. Key determinants of the cellular repertoire of ETS proteins are their stability and turnover, controlled largely by the actions of selective E3 ubiquitin ligases and deubiquitinases. Here we discuss the known relationships between ETS proteins and enzymes that determine their ubiquitin status, their integration with other developmental signal transduction pathways and how suppression of ETS protein ubiquitination contributes to the malignant cell phenotype in multiple cancers.
  • 820
  • 21 Jul 2021
Topic Review Video
Transgenerational-Epigenetic Inheritance and Immune System
Epigenetic modifications cause heritable changes in gene expression which are not due to alterations in underlying DNA sequence. Inside the eukaryotic nucleus, there is condense packing of DNA around histone proteins to constitute chromatin structure. Epigenetic modifications are caused by factors that alter chromatin structure. Some epigenetic factors are enzymes that regulate DNA methylation and histone modifications, non-coding RNA, and prions. An offspring inherits parental epigenetic modifications but most of them are deleted and reset during early developmental stages. Some epigenetic modifications are retained and persist across multiple generations. If any epigenetic modification is the result of a stimulus or immune response in one generation, such that the modification continues to be inherited in subsequent generations which are not subjected to the stimulus; and the inheritance continues beyond the 3rd generation in the female germline and 2nd generation in male, then the phenomenon is called transgenerational epigenetic inheritance (TGEI). This entry is focused on a review which discusses some examples of TGEI that are reported in association with  immune system development and disorders.
  • 810
  • 22 May 2021
Topic Review
Human Heart Organoid Development
The emergence of human-induced Pluripotent Stem Cells (hiPSCs) has dramatically improved the understanding of human developmental processes under normal and diseased conditions. The hiPSCs have been differentiated into various tissue-specific cells in vitro, and the advancement in three-dimensional (3D) culture has provided a possibility to generate those cells in an in vivo-like environment. Tissues with 3D structures can be generated using different approaches such as self-assembled organoids and tissue-engineering methods, such as bioprinting. Researchers are interested in studying the self-assembled organoids differentiated from hiPSCs, as they have the potential to recapitulate the in vivo developmental process and be used to model human development and congenital defects. Organoids of tissues such as those of the intestine and brain were developed many years ago, but heart organoids were not reported until recently.
  • 801
  • 10 May 2022
Topic Review
Genetics Matters
The understanding of how genetic information may be inherited through generations was established by Gregor Mendel in the 1860s when he developed the fundamental principles of inheritance. The science of genetics, however, began to flourish only during the mid-1940s when DNA was identified as the carrier of genetic information. The world has since then witnessed rapid development of genetic technologies, with the latest being genome-editing tools, which have revolutionized fields from medicine to agriculture. This entry walks through the historical timeline of genetics research and deliberates how this discipline might furnish a sustainable future for humanity.
  • 789
  • 19 Apr 2022
Topic Review
Regulation of Hedgehog Signal Transduction
The Hedgehog (Hh) family of secreted proteins governs embryonic development and adult tissue homeostasis in species ranging from insects to mammals. Deregulation of Hh pathway activity has been implicated in a wide range of human disorders, including congenital diseases and cancer. Hh exerts its biological influence through a conserved signaling pathway. Binding of Hh to its receptor Patched (Ptc), a twelve-span transmembrane protein, leads to activation of an atypical GPCR family protein and Hh signal transducer Smoothened (Smo), which then signals downstream to activate the latent Cubitus interruptus (Ci)/Gli family of transcription factors. Hh signal transduction is regulated by ubiquitination and deubiquitination at multiple steps along the pathway including regulation of Ptc, Smo and Ci/Gli proteins. 
  • 781
  • 15 Dec 2021
Topic Review
Autonomy in Stem Cell-Derived Embryoids
The experimental production of complex structures resembling mammalian embryos (e.g., blastoids, gastruloids) from pluripotent stem cells in vitro has become a booming research field. Since some of these embryoid models appear to reach a degree of complexity that may come close to viability, a broad discussion has set in with the aim to arrive at a consensus on the ethical implications with regard to acceptability of the use of this technology with human cells. The present text focuses on developmental autonomy of embryoids which is an aspect of great ethical relevance and must receive increased attention during the preparation of new legal regulations, but which has not been included yet in the recently issued ISSCR Guidelines.  
  • 781
  • 10 Nov 2021
Topic Review
Aperture Formation in Angiosperms
Apertures are the areas where the exine is thinner or even lacking. A great diversity in pollen grain morphology is observed in angiosperms.
  • 777
  • 18 Feb 2022
Topic Review
Development of Schwann Cells
Schwann cells are glial cells of the peripheral nervous system. They exist in several subtypes and perform a variety of functions in nerves. Their derivation and culture in vitro are interesting for applications ranging from disease modeling to tissue engineering. Since primary human Schwann cells are challenging to obtain in large quantities, in vitro differentiation from other cell types presents an alternative. To achieve differentiation of Schwann cells from stem cell sources in vitro, cultures are manipulated using molecular factors to emulate developmental signaling events which lead to development of Schwann cells in vivo. Therefore, knowledge of molecular determinants in embryonal development of the Schwann cell fate is key to develop and refine in vitro differentiation protocols.
  • 775
  • 05 Dec 2022
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