Assembloid
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Assembloid
An assembloid is an ''in vitro'' model that combines two or more organoids, spheroids, or cultured cell types to recapitulate structural and functional properties of an organ. They are typically derived from induced pluripotent stem cells. Assembloids have been used to study cell migration, neural circuit assembly, neuro-immune interactions, metastasis, and other complex tissue processes. The term "assembloid" was coined by Sergiu P. Pașca's lab in 2017. Generation of assembloids Assembloids were described in 2017 in a study from a laboratory at Stanford to model forebrain development. Assembloids joining ventral and dorsal forebrain neural organoids demonstrated that cortical interneurons migrate and integrate into synaptically connected cortical microcircuits. This was confirmed by multiple research groups applying similar approaches to model regionalized organoid interactions and study interneuron migration. Assembloids have subsequently been generated to model projection ...
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In Vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology and its subdisciplines are traditionally done in labware such as test tubes, flasks, Petri dishes, and microtiter plates. Studies conducted using components of an organism that have been isolated from their usual biological surroundings permit a more detailed or more convenient analysis than can be done with whole organisms; however, results obtained from ''in vitro'' experiments may not fully or accurately predict the effects on a whole organism. In contrast to ''in vitro'' experiments, ''in vivo'' studies are those conducted in living organisms, including humans, and whole plants. Definition ''In vitro'' ( la, in glass; often not italicized in English usage) studies are conducted using components of an organism that have been isolated fro ...
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Forebrain
In the anatomy of the brain of vertebrates, the forebrain or prosencephalon is the Anatomical terms of location#Directional terms, rostral (forward-most) portion of the brain. The forebrain (prosencephalon), the midbrain (mesencephalon), and hindbrain (rhombencephalon) are the three Brain vesicle, primary brain vesicles during the early development of the nervous system. The forebrain controls body temperature, reproductive functions, eating, sleeping, and the display of emotions. At the five-vesicle stage, the forebrain separates into the diencephalon (thalamus, hypothalamus, subthalamus, and epithalamus) and the telencephalon which develops into the cerebrum. The cerebrum consists of the cerebral cortex, underlying white matter, and the basal ganglia. In humans, by 5 weeks in utero it is visible as a single portion toward the front of the fetus. At 8 weeks in utero, the forebrain splits into the left and right cerebral hemispheres. When the embryonic forebrain fails to divide ...
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Induced Pluripotent Stem Cells
Induced pluripotent stem cells (also known as iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from a somatic cell. The iPSC technology was pioneered by Shinya Yamanaka's lab in Kyoto, Japan, who showed in 2006 that the introduction of four specific genes (named Myc, Oct3/4, Sox2 and Klf4), collectively known as Yamanaka factors, encoding transcription factors could convert somatic cells into pluripotent stem cells. He was awarded the 2012 Nobel Prize along with Sir John Gurdon "for the discovery that mature cells can be reprogrammed to become pluripotent." Pluripotent stem cells hold promise in the field of regenerative medicine. Because they can propagate indefinitely, as well as give rise to every other cell type in the body (such as neurons, heart, pancreatic, and liver cells), they represent a single source of cells that could be used to replace those lost to damage or disease. The most well-known type of pluripotent stem cell is the ...
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Myelinoid
A myelinoid or myelin organoid is a three dimensional ''in vitro'' cultured model derived from human pluripotent stem cells (hPSCs) that represents various brain regions, the spinal cord or the peripheral nervous system in early fetal human development. Myelinoids have the capacity to recapitulate aspects of brain developmental processes, microenvironments, cell to cell interaction, structural organization and cellular composition. The differentiating aspect dictating whether an organoid is deemed a cerebral organoid/brain organoid or myelinoid is the presence of myelination and compact myelin formation that is a defining feature of myelinoids. Due to the complex nature of the human brain, there is a need for model systems which can closely mimic complicated biological processes. Myelinoids provide a unique ''in vitro'' model through which myelin pathology, neurodegenerative diseases, developmental processes and therapeutic screening can be accomplished. History ''In vitro'' mod ...
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Organoid
An organoid is a miniaturized and simplified version of an Organ (anatomy), organ produced in vitro in three dimensions that shows realistic micro-anatomy. They are derived from one or a few Cell (biology), cells from a Tissue (biology), tissue, embryonic stem cells or induced pluripotent stem cells, which can Self-organization, self-organize in three-dimensional culture owing to their Stem cell, self-renewal and Cellular differentiation, differentiation capacities. The technique for growing organoids has rapidly improved since the early 2010s, and it was named by ''The Scientist (magazine), The Scientist'' as one of the biggest scientific advancements of 2013. Organoids are used by scientists to study disease and treatments in a laboratory. History Attempts to create organ (biology), organs ''in vitro'' started with one of the first dissociation-reaggregation experiments where Henry Van Peters Wilson demonstrated that mechanically dissociated sponge cells can reaggregate and se ...
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Apolipoprotein E
Apolipoprotein E (APOE) is a protein involved in the metabolism of fats in the body of mammals. A subtype is implicated in Alzheimer's disease and cardiovascular disease. APOE belongs to a family of fat-binding proteins called apolipoproteins. In the circulation, it is present as part of several classes of lipoprotein particles, including chylomicron remnants, VLDL, IDL, and some HDL. APOE interacts significantly with the low-density lipoprotein receptor (LDLR), which is essential for the normal processing (catabolism) of triglyceride-rich lipoproteins. In peripheral tissues, APOE is primarily produced by the liver and macrophages, and mediates cholesterol metabolism. In the central nervous system, APOE is mainly produced by astrocytes and transports cholesterol to neurons via APOE receptors, which are members of the low density lipoprotein receptor gene family. APOE is the principal cholesterol carrier in the brain. APOE is required for cholesterol transportation from astrocy ...
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Alzheimer's Disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term memory, remembering recent events. As the disease advances, symptoms can include primary progressive aphasia, problems with language, Orientation (mental), disorientation (including easily getting lost), mood swings, loss of motivation, self-neglect, and challenging behaviour, behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the typical life expectancy following diagnosis is three to nine years. The cause of Alzheimer's disease is poorly understood. There are many environmental and genetic risk factors associated with its development. The strongest genetic risk factor is from an alle ...
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Rett Syndrome
Rett syndrome (RTT) is a genetic disorder that typically becomes apparent after 6–18 months of age and almost exclusively in females. Symptoms include impairments in language and coordination, and repetitive movements. Those affected often have slower growth, difficulty walking, and a smaller head size. Complications of Rett syndrome can include seizures, scoliosis, and sleeping problems. The severity of the condition is variable. Rett syndrome is due to a genetic mutation in the MECP2 gene, on the X chromosome. It almost always occurs as a new mutation, with less than one percent of cases being inherited from a person's parents. It occurs almost exclusively in girls; boys who have a similar mutation typically die shortly after birth. Diagnosis is based on the symptoms and can be confirmed with genetic testing. There is no known cure for Rett syndrome. Treatment is directed at improving symptoms. Anticonvulsants may be used to help with seizures. Special education, ph ...
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22q13 Deletion Syndrome
22q13 deletion syndrome, also known as Phelan–McDermid syndrome (PMS), is a genetic disorder caused by deletions or rearrangements on the q terminal end (long arm) of chromosome 22. Any abnormal genetic variation in the q13 region that presents with significant manifestations (phenotype) typical of a terminal deletion may be diagnosed as 22q13 deletion syndrome. There is disagreement among researchers as to the exact definition of 22q13 deletion syndrome. The Developmental Synaptopathies Consortium defines PMS as being caused by ''SHANK3'' mutations, a definition that appears to exclude terminal deletions. The requirement to include ''SHANK3'' in the definition is supported by many but not by those who first described 22q13 deletion syndrome. Prototypical terminal deletion of 22q13 can be uncovered by karyotype analysis, but many terminal and interstitial deletions are too small. The availability of DNA microarray technology for revealing multiple genetic problems simultaneousl ...
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L-type Calcium Channel
The L-type calcium channel (also known as the dihydropyridine channel, or DHP channel) is part of the high-voltage activated family of voltage-dependent calcium channel. "L" stands for long-lasting referring to the length of activation. This channel has four isoforms: Cav1.1, Cav1.2, Cav1.3, and Cav1.4. L-type calcium channels are responsible for the excitation-contraction coupling of skeletal, smooth, cardiac muscle, and for aldosterone secretion in endocrine cells of the adrenal cortex. They are also found in neurons, and with the help of L-type calcium channels in endocrine cells, they regulate neurohormones and neurotransmitters. They have also been seen to play a role in gene expression, mRNA stability, neuronal survival, ischemic-induced axonal injury, synaptic efficacy, and both activation and deactivation of other ion channels. In cardiac myocytes, the L-type calcium channel passes inward Ca2+ current (ICaL) and triggers calcium release from the sarcoplasmic reticul ...
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Timothy Syndrome
Timothy syndrome is a rare autosomal-dominant disorder characterized by physical malformations, as well as neurological and developmental defects, including heart QT-prolongation, heart arrhythmias, structural heart defects, syndactyly (webbing of fingers and toes), and autism spectrum disorders. Timothy syndrome represents one clinical manifestation of a range of disorders associated with mutations in ''CACNA1C'', the gene encoding the calcium channel Cav1.2 α subunit. Signs and symptoms The most striking sign of Timothy syndrome type 1 is the co-occurrence of both syndactyly (about 0.03% of births) and long QT syndrome (1% per year) in a single patient. Other common symptoms include cardiac arrhythmia (94%), heart malformations (59%), and autism or an autism spectrum disorder (80% who survive long enough for evaluation). Facial dysmorphologies such as flattened noses also occur in about half of patients. Children with this disorder have small teeth, which is due to poor ena ...
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Neural Crest
Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, peripheral and enteric neurons and glia. After gastrulation, neural crest cells are specified at the border of the neural plate and the non-neural ectoderm. During neurulation, the borders of the neural plate, also known as the neural folds, converge at the dorsal midline to form the neural tube. Subsequently, neural crest cells from the roof plate of the neural tube undergo an epithelial to mesenchymal transition, delaminating from the neuroepithelium and migrating through the periphery where they differentiate into varied cell types. The emergence of neural crest was important in vertebrate evolution because many of its structural derivatives are defining features of the vertebrate clade. Underlying the development of neural crest is ...
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