Stem Cell Glossary – Closer Look at Stem Cells

Stem cell science involves many technical terms. This glossary covers many of the common terms you will encounter in reading about stem cells.

Adult stem cells A commonly used term for tissue-specific stem cells, cells that can give rise to the specialized cells in specific tissues. Includes all stem cells other than pluripotent stem cells such as embryonic and induced pluripotent stem cells.

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Autologous Cells or tissues from the same individual; an autologous bone marrow transplant involves one individual as both donor and recipient.

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Basic research Research designed to increase knowledge and understanding (as opposed to research designed with the primary goal to solve a problem).

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Blastocyst A transient, hollow ball of 150 to 200 cells formed in early embryonic development that contains the inner cell mass, from which the embryo develops, and an outer layer of cell called the trophoblast, which forms the placenta.

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Bone marrow stromal cells A general term for non-blood cells in the bone marrow, such as fibroblasts, adipocytes (fat cells) and bone- and cartilage-forming cells that provide support for blood cells. Contained within this population of cells are multipotent bone marrow stromal stem cells that can self-renew and give rise to bone, cartilage, adipocytes and fibroblasts.

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Cardiomyocytes The functional muscle cells of the heart that allow it to beat continuously and rhythmically.

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Clinical translation The process of using scientific knowledge to design, develop and apply new ways to diagnose, stop or fix what goes wrong in a particular disease or injury; the process by which basic scientific research becomes medicine.

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Clinical trial Tests on human subjects designed to evaluate the safety and/or effectiveness of new medical treatments.

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Cord blood The blood in the umbilical cord and placenta after child birth. Cord blood contains hematopoietic stem cells, also known as cord blood stem cells, which can regenerate the blood and immune system and can be used to treat some blood disorders such as leukemia or anemia. Cord blood can be stored long-term in blood banks for either public or private use. Also called umbilical cord blood.

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Cytoplasm Fluid inside a cell, but outside the nucleus.

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Differentiation The process by which cells become increasingly specialized to carry out specific functions in tissues and organs.

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Drug discovery The systematic process of discovering new drugs.

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Drug screening The process of testing large numbers of potential drug candidates for activity, function and/or toxicity in defined assays.

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Embryo Generally used to describe the stage of development between fertilization and the fetal stage; the embryonic stage ends 7-8 weeks after fertilization in humans.

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Embryonic stem cells (ESCs) Undifferentiated cells derived from the inner cell mass of the blastocyst; these cells have the potential to give rise to all cell types in the fully formed organism and undergo self-renewal.

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Fibroblast A common connective or support cell found within most tissues of the body.

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Glucose A simple sugar that cells use for energy.

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Hematopoietic Blood-forming; hematopoietic stem cells give rise to all the cell types in the blood.

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Immunomodulatory The ability to modify the immune system or an immune response.

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Induced pluripotent stem cells (iPSCs) Embryonic-like stem cells that are derived from reprogrammed, adult cells, such as skin cells. Like ESCs, iPS cells are pluripotent and can self-renew.

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In vitro Latin for in glass. In biomedical research this refers to experiments that are done outside the body in an artificial environment, such as the study of isolated cells in controlled laboratory conditions (also known as cell culture).

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In vivo Latin for within the living. In biomedical research this refers to experiments that are done in a living organism. Experiments in model systems such as mice or fruit flies are an example of in vivo research.

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Islets of Langerhans Clusters in the pancreas where insulin-producing beta cells live.

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Macula A small spot at the back of the retina, densely packed with the rods and cones that receive light, which is responsible for high-resolution central vision.

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Mesenchymal stem cells (MSCs) A term used to describe cells isolated from the connective tissue that surrounds other tissues and organs. MSCs were first isolated from the bone marrow and shown to be capable of making bone, cartilage and fat cells. MSCs are now grown from other tissues, such as fat and cord blood. Not all MSCs are the same and their characteristics depend on where in the body they come from and how they are isolated and grown. May also be called mesenchymal stromal cells.

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Multipotent stem cells Stem cells that can give rise to several different types of specialized cells in specific tissues; for example, blood stem cells can produce the different types of cells that make up the blood, but not the cells of other organs such as the liver or the brain.

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Neuron An electrically excitable cell that processes and transmits information through electrical and chemical signals in the central and peripheral nervous systems.

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Pancreatic beta cells Cells responsible for making and releasing insulin, the hormone responsible for regulating blood sugar levels. Type I diabetes occurs when these cells are attacked and destroyed by the body's immune system.

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Photoreceptors Rod or cone cells in the retina that receive light and send signals to the optic nerve, which passes along these signals to the brain.

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Placebo A pill, injection or other treatment that has no therapeutic benefit; often used as a control in clinical trials to see whether new treatments work better than no treatment.

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Placebo effect Perceived or actual improvement in symptoms that cannot be attributed to the placebo itself and therefore must be the result of the patient's (or other interested person's) belief in the treatment's effectiveness.

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Pluripotent stem cells Stem cells that can become all the cell types that are found in an embryo, fetus or adult, such as embryonic stem cells or induced pluripotent (iPS) cells.

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Preclinical research Laboratory research on cells, tissues and/or animals for the purpose of discovering new drugs or therapies.

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Precursor cells An intermediate cell type between stem cells and differentiated cells. Precursor cells have the potential to give rise to a limited number or type of specialized cells. Also called progenitor cells.

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Progenitor cells An intermediate cell type between stem cells and differentiated cells. Progenitor cells have the potential to give rise to a limited number or type of specialized cells and have a reduced capacity for self-renewal. Also called precursor cells.

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Regenerative Medicine An interdisciplinary branch of medicine with the goal of replacing, regenerating or repairing damaged tissue to restore normal function. Regenerative treatments can include cellular therapy, gene therapy and tissue engineering approaches.

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Reprogramming In the context of stem cell biology, this refers to the conversion of differentiated cells, such as fibroblasts, into embryonic-like iPS cells by artificially altering the expression of key genes.

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Retinal pigment epithelium A single-cell layer behind the rods and cones in the retina that provide support functions for the rods and cones.

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RNA Ribonucleic acid; it "reads" DNA and acts as a messenger for carrying out genetic instructions.

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Scientific method A systematic process designed to understand a specific observation through the collection of measurable, empirical evidence; emphasis on measurable and repeatable experiments and results that test a specific hypothesis.

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Self-renewal A special type of cell division in stem cells by which they make copies of themselves.

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Somatic stem cells Scientific term for tissue-specific or adult stem cells.

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Stem cells Cells that have both the capacity to self-renew (make more stem cells by cell division) and to differentiate into mature, specialized cells.

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Stem cell tourism The travel to another state, region or country specifically for the purpose of undergoing a stem cell treatment available at that location. This phrase is also used to refer to the pursuit of untested and unregulated stem cell treatments.

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Teratoma A benign tumor that usually consists of several types of tissue cells that are foreign to the tissue in which the tumor is located.

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Tissue A group of cells with a similar function or embryological origin. Tissues organize further to become organs.

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Tissue-specific stem cells Stem cells that can give rise to the specialized cells in specific tissues; blood stem cells, for example, can produce the different types of cells that make up the blood, but not the cells of other organs such as the liver or the brain. Includes all stem cells other than pluripotent stem cells such as embryonic and induced pluripotent cells. Also called adult or somatic stem cells.

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Totipotent The ability to give rise to all the cells of the body and cells that arent part of the body but support embryonic development, such as the placenta and umbilical cord.

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Translational research Research that focuses on how to use knowledge gleaned from basic research to develop new drugs, treatments or therapies.

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Zygote The single cell formed when a sperm cell fuses with an egg cell.

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Stem Cell Glossary - Closer Look at Stem Cells

What are induced pluripotent stem cells or iPS cells? – Stem …

In November 2007 scientists announced they had developed a new way to cause mature human cells to resemble pluripotent stem cells - similar in many ways to human embryonic stem cells. By simply altering the expression of just four genes using genetic modification, the mature cells were 'induced' to become more primitive, stem cells and were referred to as 'induced' pluripotent stem (iPS) cells.

Initially iPS cells were generated using viruses to change gene expression, however since the initial discovery, technologies for reprogramming cells are moving very quickly and researchers are now investigating the use of new methods that do not use viruses which can cause permanent and potentially harmful changes in the cells. If they are able to be made safely, and on a large scale, iPS cells could possibly be used to provide a source of cells to replace cells damaged following illness or disease. It may even be possible to make stem cells for therapy from a patient's own cells and thereby avoid the use of anti-rejection medications.

However, right now scientists are using this method to create disease specific cells for research by taking a cells - maybe from a skin biopsy - from a patient with a genetic disorder, such as Huntingtons disease, and then using the iPS cells to study the disease in the laboratory. Scientist hope that such an approach will help them understand the development and progression of certain diseases, and assist in the development and testing of new drugs to treat disease.

While the discovery of iPS cells was a very important development, more research needs to be done to discover if they will offer the same research value as embryonic stem cells and if they will be as useful for therapy.

To learn more about iPS cells watch What are induced pluripotent stem cells? in our video library.

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What are induced pluripotent stem cells or iPS cells? - Stem ...

A New Epigenetic Barrier to Induced Pluripotent Stem Cells – WhatIsEpigenetics.com

By adding theright concoction of ingredients, scientists can reprogram youreverydaysomatic cell intoan inducedpluripotentstemcell(IPSC) that is,aculturedcellthat has the ability todifferentiate into almost any othercelltypein response to specificenvironmentalfactors, similar to an embryonic stem cell. Thisinnovativetechnology allows the study of the molecularmechanismsofearlydevelopmentanddisease,withouttheethical restrictionsassociated withembryonic stem cells.

Not surprisingly, the possibility of utilizing induced pluripotent stem cells in the field of regenerative medicine is of important focus to many scientists. In a recent post, we touched on the potential ability of vitamins A and C to enhance the erasure of epigenetic memory required for cell reprogramming. Because these special types of cells can propagate indefinitely and form any other cell type in the body such as neurons, liver, and heart cells we may be able to replace lost organs, repair tissue, and even generate type O red blood cells, which can be used in transfusions for people with any blood type.

Greatso whats the problem?

Unfortunately, thereare drawbacksto this technology, namely the efficiency of reprogramming.Many IPSCsdo not actually gain completepluripotency. Epigenetic modifications are heavily implicated during the reprogramming process whereby the epigenetic makeup of the cell is completely overhauledto first encourage the expression of pluripotent genes and thenremodelled to encourage the expression of genes associated withthefinalcell typethattheIPSCwillbecome. As the epigenome plays a crucial role inreprogramming,inconsistenciesof pluripotencyacrossIPSClinesmaybedue toepigenetic barriers.

TRIM28: a novel epigenetic barrier

A team of scientists headed by Dr. Miles from The Netherlands Cancer institute recently uncovered a novel epigenetic barrier to the efficient induction of pluripotent stem cell reprogramming. Published in a recent issue of STEM CELLS, the paper highlights the use of a shRNA screen targeting over 670 epigenetic modifiers, revealing the involvement of TRIM28 in the resistance of cells transitioning from somatic to pluripotent state.

TRIM28, or Tripartite motif-containing 28, is involved in mediating transcriptional control by interacting with a certain domain in numerous transcription factors. Previous research shows that it plays a role in cellular differentiation and proliferation, DNA damage repair response, transcriptional regulation, and apoptosis.

By blocking the expression TRIM28 during reprogramming, the group demonstrated increases in the number of cells reaching pluripotency, as well as increased expression of a selection of 143 genes.

Analysis of the list of genes revealed the most statistically significant gene ontology term was unclassified. This result indicates TRIM28 does not regulate a specific pathway during reprogramming, states the authors.

It is known that TRIM28 gene encodes for a protein known to be involved in transcriptional regulation via the recruitment and formation of protein complexes that maintain repressive chromatin. Given this, researchers proposed the gene expression alterations, hence reprogramming differences, were likely to be associated with chromatin modification.

SEE ALSO: Maternal Smoking Epigenetically Harms Child Development

Subsequent tests supported this notion by establishing a proportion of the 143 genes to be located near H3K9me3 a repressive histone H3 modification which has shown to influence the transcription of genes that impedes the IPSC reprogramming process. When TRIM28 expression was blocked, the closer genes are to the H3K9me3 the greater the increase in expression. This suggests the role of TRIM28 in repressing the expression of genes involved in reprogramming via the maintenance of H3K9me3 heterochromatin site.

Whyis this important?

Due to the potential to produce almost anyothertype of cell, thetechnology ofIPSChas sparked excitement in the clinical sciences. The implementation ofIPSCto repair damaged or diseased tissue or to test/develop personalised medicines ison the horizon.By establishing barriers preventing the efficient transition of differentiated cells to pluripotent cells scientist canrefineIPSC generationto make the future clinical use ofIPSCsboth safe and efficient.

Source: Miles, D. C., de Vries, N. A., Gisler, S., Lieftink, C., Akhtar, W., Gogola, E., & Beijersbergen, R. L. (2017). TRIM28 is an Epigenetic Barrier to Induced Pluripotent Stem Cell Reprogramming.STEM CELLS,35(1), 147-157.

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A New Epigenetic Barrier to Induced Pluripotent Stem Cells - WhatIsEpigenetics.com

Is it time to start worrying about conscious human mini-brains? – PLoS Blogs (blog)

A human iPSC cerebral organoid in which pigmented retinal epithelial cells can be seen (from the work of McClure-Begley, Mike Klymkowsky, and William Old.)

The fact that experiments on people are severely constrained is a major obstacle in understanding human development and disease. Some of these constraints are moral and ethical and clearly appropriate and necessary given the depressing history of medical atrocities. Others are technical, associated with the slow pace of human development. The combination of moral and technical factors has driven experimental biologists to explore the behavior of a wide range of model systems from bacteria, yeasts, fruit flies, and worms to fish, frogs, birds, rodents, and primates. Justified by the deep evolutionary continuity between these organisms (after all, all organisms appear to be descended from a single common ancestor and share many molecular features), experimental evolution-based studies of model systems have led to many therapeutically valuable insights in humans something that I suspect a devotee of intelligent design creationism would be hard pressed to predict or explain (post link).

While humans are closely related to other mammals, it is immediately obvious that there are important differences after all people are instantly recognizable from members of other closely related species and certainly look and behave differently from mice. For example, the surface layer of our brains are extensively folded (they are known as gyrencephalic) while the brain of a mouse is smooth as a babys bottom (and referred to as lissencephalic). In humans, the failure of the brain cortex to fold is known as lissencephaly, a disorder associated with several severe neurological defects. With the advent of more and more genomic sequence data, we can identify human specific molecular (genomic) differences. Many of these sequence differences occur in regions of our DNA that regulate when and where specific genes are expressed. Sholtis & Noonan (1) provide an example: the HACNS1 locus is a 81 basepair region that is highly conserved in various vertebrates from birds to chimpanzees; there are 13 human specific changes in this sequence that appear to alter its activity, leading to human-specific changes in the expression of nearby genes (). At this point ~1000 genetic elements that are different in humans compared to other vertebrates have been identified and more are likely to emerge (2). Such human-specific changes can make modeling human-specific behaviors, at the cellular, tissue, organ, and organism level, in non-human model systems difficult and problematic (3,4). It is for this reason that scientists have attempted to generate better human specific systems.

One particularly promising approach is based on what are known as embryonic stem cells (ESCs) or pluripotent stem cells (PSCs). Human embryonic stem cells are generated from the inner cell mass of a human embryo and so involve the destruction of that embryo which raises a number of ethical and religious concerns as to when life begins (5)(more on that in a future post). Human pluripotent stem cells are isolated from adult tissues but in most cases require invasive harvesting methods that limit their usefulness. Both ESCs and PSCs can be grown in the laboratory and can be induced to differentiate into what are known as gastruloids. Such gastruloids can develop anterior-posterior (head-tail), dorsal-ventral (back-belly), and left-right axes analogous to those found in embryos (6) and adults (top panel). In the case of PSCs, the gastruloid (bottom panel ) is essentially a twin of the organism from which the PSCs were derived, a situation that raises difficult questions: is it a distinct individual, is it the property of the donor or the creation of a technician. The situation will be further complicated if (or rather, when) it becomes possible to generate viable embryos from such gastruloids.

The Nobel prize winning work of Kazutoshi Takahashi and Shinya Yamanaka (7), who devised methods to take differentiated (somatic) human cells and reprogram them into ESC/PSC-like cells, cells known as induced pluripotent stem cells (iPSCs)(8), represented a technical breakthrough that jump-started this field. While the original methods derived sample cells from tissue biopsies, it is possible to reprogramkidney epithelial cells recovered from urine, a non-invasive approach (9,10). Subsequently, Madeline Lancaster, Jurgen Knblich, and colleagues devised an approach by which such cells could be induced to form what they termed cerebral organoids; they used thismethod to examine the developmental defects associated with microencephaly (11). The value of the approach was rapidly recognized and a number of studies on human conditions, including lissencephaly (12), Zika-virus infection-induced microencephaly(13), and Downs syndrome (14); investigatorshave begun to exploit these methodsto study a range of human diseases.

The production of cerebral organoids from reprogrammed human somatic cells has also attracted the attention of the media (15). While mini-brain is certainly a catchier name, it is a less accurate description of a cerebral organoid, itself possibly a bit of an overstatement, since it is not clear exactly how cerebral such organoids are. For example, the developing brain is patterned by embryonic signals that establish its asymmetries; it forms at the anterior end of the neural tube (the nascent central nervous system and spinal cord) and with distinctive anterior-posterior, dorsal-ventral, and left-right asymmetries, something that simple cerebral organoids do not display. Moreover, current methods for generating cerebral organoids involve primarily what are known as neuroectodermal cells our nervous system (and that of other vertebrates) is a specialized form of the embryos surface layer that gets internalized during development. In the embryo, the developing neuroectoderm interacts with cells of the circulatory system (capillaries, veins, and arteries), formed by endothelial cells and what are known as pericytes that surround them. These cells, together with interactions with glial cells (astrocytes, a non-neuronal cell type) combine to form the blood brain barrier. Other glial cells (oligodendrocytes) are also present; in contrast, both types of glia (astrocytes and oligodendrocytes) are rare in the current generation of cerebral organoids. Finally, there are microglial cells, immune system cells that originate from outside the neuroectoderm; they invade and interact with neurons and glia as part of the brains dynamic neural system. The left panel of the figure shows, in highly schematic form how these cells interact (16). The right panel is a drawing of neural tissue stained by the Golgi method (17), which reveals~3-5% of the neurons present. There are at least as many glial cells present, as well as microglia, none of which are visible in the image. At this point, cerebral organoids typically contain few astrocytes and oligodendrocytes, no vasculature, and no microglia. Moreover, they grow to be about 1 to 3 mm in diameter over the course of 6 to 9 months; that is significantly smaller in volume than a fetal or newborns brain. While cerebral organoids can generate structures characteristic of retinal pigment epithelia (top figure) and photo-responsive neurons (18), such as those associated with the retina, an extension of the brain, it is not at all clear that there is any significant sensory input into the neuronal networks that are formed within a cerebral organoid, or any significant outputs, at least compared to the role that the human brain plays in controlling bodily and mental functions.

The reasonable question, then, must be whether a cerebral organoid, which is a relatively simple system of cells (although itself complex), is conscious. It becomes more reasonable as increasingly complex systems are developed, and such work is proceeding apace. Already researchers are manipulating the developing organoids environment to facilitate axis formation, and one can anticipate the introduction of vasculature. Indeed, the generation of microglia-like cells from iPSCs has been reported; such cells can be incorporated into cerebral organoids where they appear to respond to neuronal damage in much the same way as microglia behave in intact neural tissue (19).

We can ask ourselves, what would convince us that a cerebral organoid, living within a laboratory incubator, was conscious? How would such consciousnessmanifest itself? Through some specific pattern of neural activity, perhaps? As a biologist, albeit one primarily interested in molecular and cellular systems, I discount the idea, proposed by some physicists and philosophers as well as the more mystical, that consciousness is a universal property of matter (20,21). I take consciousness to be an emergent property of complex neural systems, generated by evolutionary mechanisms, builtduring embryonic and subsequent development, and influenced bysocial interactions (BLOG LINK) using information encoded within the human genome (something similar to this: A New Theory Explains How Consciousness Evolved). While a future concern, in a world full of more immediate and pressing issues, it will be interesting to listen to the academic, social, and political debate on what to do with mini-brains as they grow in complexity and perhaps inevitably, towards consciousness.

Footnotes and references

Thanks to Rebecca Klymkowsky, Esq. and Joshua Sanes, Ph.D. for editing anddisciplinarysupport.

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Is it time to start worrying about conscious human mini-brains? - PLoS Blogs (blog)