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Topic review
Updated time: 15 Nov 2021
Submitted by: Terisha Ghazi
Definition: 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.
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Topic review
Updated time: 23 Nov 2021
Submitted by: Alexandra Rippa
Definition: 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.
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Topic review
Updated time: 10 Nov 2021
Submitted by: Hans-Werner Denker
Definition: 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.
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Topic review
Updated time: 17 Nov 2021
Submitted by: Yin Lau Lee
Definition: Pluripotent stem cells (PSCs) hold great promise in cell-based therapy because of their pluripotent property and the ability to proliferate indefinitely. Embryonic stem cells (ESCs) derived from inner cell mass (ICM) possess unique cell cycle control with shortened G1 phase. In addition, ESCs have high expression of homologous recombination (HR)-related proteins, which repair double-strand breaks (DSBs) through HR or the non-homologous end joining (NHEJ) pathway.
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Topic review
Updated time: 28 Oct 2021
Submitted by: Asim Bepari
Definition: Three ADF/cofilin family members are expressed in mammals: ADF, cofilin-1, and cofilin-2. The first member ADF (also known as destrin), encoded by the gene DSTN in humans, was initially identified in the chick brain. Cofilin was discovered as an actin-interacting protein in the porcine brain. Later, Ono et al. identified two mammalian variants of cofilin, non-muscle type (also known as cofilin-1 and n-cofilin) and muscle type (also known as cofilin-2 and m-cofilin). In humans, cofilin-1 and cofilin-2 are encoded by the genes CFL1 and CFL2, respectively. Different isoforms of ADF/cofilin have qualitatively similar but quantitatively different effects on actin dynamics. To be noted, both ADF and cofilin show cooperative binding with actin filaments. Interestingly, cofilin-1 comprises almost 90% of the total ADF/cofilin family in CNS.Cofilin can bind to both G-actin and F-actin, exhibiting stronger affinities for the ADP-bound actins than the ATP- or ADP-Pi-bound forms. Cofilin binding to F-actin induces actin subunit rotation, enhances Pi release along the filament, and promotes filament severing in a concentration-dependent manner.
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Topic review
Updated time: 30 Nov 2021
Submitted by: Rute Moura
Definition: 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.
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Topic review
Updated time: 12 Oct 2021
Submitted by: Shailendra Maurya
Definition: Enhancers are cis-regulatory elements containing short DNA sequences that serve as binding sites for pioneer/regulatory transcription factors, thus orchestrating the regulation of genes critical for lineage determination. The activity of enhancer elements is believed to be determined by transcription factor binding, thus determining the cell state identity during development. Precise spatio-temporal control of the transcriptome during lineage specification requires the coordinated binding of lineage-specific transcription factors to enhancers. Thus, enhancers are the primary determinants of cell identity. Numerous studies have explored the role and mechanism of enhancers during development and disease, and various basic questions related to the functions and mechanisms of enhancers have not yet been fully answered.
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Topic review
Updated time: 27 Oct 2021
Submitted by: Chiara Bruckmann
Definition: MEIS1 is highly expressed in the bone marrow, and its predominant and better-known role is in embryonic and adult hematopoiesis. Along withPBX1 and HOXA9, MEIS1 is expressed in hematopoietic stem cells (HSCs) but downregulated during their differentiation.
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Topic review
Updated time: 04 May 2021
Submitted by: Krzysztof Kobielak
Definition: Nails are highly keratinized skin appendages that exhibit continuous growth under physiological conditions and full regeneration upon removal. These mini-organs are maintained by two autonomous populations of skin stem cells. The fast-cycling, highly proliferative stem cells of the nail matrix (nail stem cells (NSCs)) predominantly replenish the nail plate. Furthermore, the slow-cycling population of the nail proximal fold (nail proximal fold stem cells (NPFSCs)) displays bifunctional properties by contributing to the peri-nail epidermis under the normal homeostasis and the nail structure upon injury. Here, we discuss nail mini-organ stem cells’ location and their role in skin and nail homeostasis and regeneration, emphasizing their importance to orchestrate the whole digit tip regeneration. Such endogenous regeneration capabilities are observed in rodents and primates. However, they are limited to the region adjacent to the nail’s proximal area, indicating the crucial role of nail mini-organ stem cells in digit restoration.
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Topic review
Updated time: 11 Oct 2021
Submitted by: Naoki Nakayama
Definition: Pluripotent stem cells (PSC) such as embryonic stem cells (ESC) and induced PSCs (iPSC) are originated from embryos and induced from adult tissue cells, respectively. PSCs are capable of proliferating almost indefinitely, and differentiating into all somatic cells, through processes that mimic early embryogenesis. The resulting cells tend to carry embryonic characteristics.
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