Model Of Early Development Research Articles

Stem cell-based models of early mammalian development.

The complex process by which a single-celled zygote develops into a viable embryo is nothing short of a miraculous wonder of the natural world. Elucidating how this process is orchestrated in humans has long eluded the grasp of scientists due to ethical and practical limitations. Thankfully, pluripotent stem cells that resemble early developmental cell types possess the ability to mimic specific embryonic events. As such, murine and human stem cells have been leveraged by scientists to create in vitro models that aim to recapitulate different stages of early mammalian development. Here, we examine the wide variety of stem cell-based embryo models that have been developed to recapitulate and study embryonic events, from pre-implantation development through to early organogenesis. We discuss the applications of these models, key considerations regarding their importance within the field, and how such models are expected to grow and evolve to achieve exciting new milestones in the future.

Early neurogenic properties of iPSC-derived neurosphere formation in Japanese macaque monkeys

Non-human primates are important models for investigations of neural development and evolution, and the use of Japanese macaque monkeys has especially contributed to the advancement of neuroscience studies. However, these studies are restricted by the number of animals able to be evaluated and the invasiveness of the methodologies. Induced pluripotent stem cells (iPSCs) can provide an alternative strategy for investigating neural development in vitro. We have established direct neurosphere (dNS) formation cultures of primate iPSCs as an in vitro model of early neurodevelopment in primate species. Here, we used dNS formation and neuronal differentiation cultures established from Japanese macaque iPSCs (jm-iPSCs) to investigate the usefulness of these cells as an in vitro model of early neural development. Time-course analyses of developmental potency and gene expression kinetics were performed during dNS formation culture of jm-iPSCs. During a 1-week culture, jm-iPSC-derived dNSs became neurogenic by day 3 and underwent stepwise expression changes of key developmental regulators along early neural development in a similar manner to chimpanzee dNS formation previously reported. Meanwhile, a subset of genes, including CYP26A1 and NPTX1, showed differential expression propensity in Japanese macaque, chimpanzee, and human iPSC-derived dNSs. Spontaneous upregulation of NOTCH signaling-associated genes HES5 and DLL1 was also observed in neuronal differentiation cultures of Japanese macaque but not chimpanzee dNSs, possibly reflecting the earlier neurogenic competence in Japanese macaques. The use of jm-iPSCs provides an alternative approach to neurological studies of primate development. Furthermore, jm-iPSCs can be used to investigate species differences in early neural development that are key to primate evolution.

Single-cell RNA-seq reveals fate determination control of an individual fibre cell initiation in cotton (Gossypium hirsutum).

Cotton fibre is a unicellular seed trichome, and lint fibre initials per seed as a factor determines fibre yield. However, the mechanisms controlling fibre initiation from ovule epidermis are not understood well enough. Here, with single-cell RNA sequencing (scRNA-seq), a total of 14 535 cells were identified from cotton ovule outer integument of Xu142_LF line at four developmental stages (1.5, 1, 0.5 days before anthesis and the day of anthesis). Three major cell types, fibre, non-fibre epidermis and outer pigment layer were identified and then verified by RNA in situ hybridization. A comparative analysis on scRNA-seq data between Xu142 and its fibreless mutant Xu142 fl further confirmed fibre cluster definition. The developmental trajectory of fibre cell was reconstructed, and fibre cell was identified differentiated at 1 day before anthesis. Gene regulatory networks at four stages revealed the spatiotemporal pattern of core transcription factors, and MYB25-like and HOX3 were demonstrated played key roles as commanders in fibre differentiation and tip-biased diffuse growth respectively. A model for early development of a single fibre cell was proposed here, which sheds light on further deciphering mechanism of plant trichome and the improvement of cotton fibre yield.

Modeling Human Cerebellar Development In Vitro in 2D Structure.

The precise and timely development of the cerebellum is crucial not only for accurate motor coordination and balance but also for cognition. In addition, disruption in cerebellar development has been implicated in many neurodevelopmental disorders, including autism, attention deficit-hyperactivity disorder (ADHD), and schizophrenia. Investigations of cerebellar development in humans have previously only been possible through post-mortem studies or neuroimaging, yet these methods are not sufficient for understanding the molecular and cellular changes occurring in vivo during early development, which is when many neurodevelopmental disorders originate. The emergence of techniques to generate human-induced pluripotent stem cells (iPSCs) from somatic cells and the ability to further re-differentiate iPSCs into neurons have paved the way for in vitro modeling of early brain development. The present study provides simplified steps toward generating cerebellar cells for applications that require a 2-dimensional (2D) monolayer structure. Cerebellar cells representing early developmental stages are derived from human iPSCs via the following steps: first, embryoid bodies are made in 3-dimensional (3D) culture, then they are treated with FGF2 and insulin to promote cerebellar fate specification, and finally, they are terminally differentiated as a monolayer on poly-l-ornithine (PLO)/laminin-coated substrates. At 35 days of differentiation, iPSC-derived cerebellar cell cultures express cerebellar markers including ATOH1, PTF1α, PAX6, and KIRREL2, suggesting that this protocol generates glutamatergic and GABAergic cerebellar neuronal precursors, as well as Purkinje cell progenitors. Moreover, the differentiated cells show distinct neuronal morphology and are positive for immunofluorescence markers of neuronal identity such as TUBB3. These cells express axonal guidance molecules, including semaphorin-4C, plexin-B2, and neuropilin-1, and could serve as a model for investigating the molecular mechanisms of neurite outgrowth and synaptic connectivity. This method generates human cerebellar neurons useful for downstream applications, including gene expression, physiological, and morphological studies requiring 2D monolayer formats.

Modeling Human Cerebellar Development <em>In Vitro</em> in 2D Structure

The precise and timely development of the cerebellum is crucial not only for accurate motor coordination and balance but also for cognition. In addition, disruption in cerebellar development has been implicated in many neurodevelopmental disorders, including autism, attention deficit-hyperactivity disorder (ADHD), and schizophrenia. Investigations of cerebellar development in humans have previously only been possible through post-mortem studies or neuroimaging, yet these methods are not sufficient for understanding the molecular and cellular changes occurring in vivo during early development, which is when many neurodevelopmental disorders originate. The emergence of techniques to generate human-induced pluripotent stem cells (iPSCs) from somatic cells and the ability to further re-differentiate iPSCs into neurons have paved the way for in vitro modeling of early brain development. The present study provides simplified steps toward generating cerebellar cells for applications that require a 2-dimensional (2D) monolayer structure. Cerebellar cells representing early developmental stages are derived from human iPSCs via the following steps: first, embryoid bodies are made in 3-dimensional (3D) culture, then they are treated with FGF2 and insulin to promote cerebellar fate specification, and finally, they are terminally differentiated as a monolayer on poly-l-ornithine (PLO)/laminin-coated substrates. At 35 days of differentiation, iPSC-derived cerebellar cell cultures express cerebellar markers including ATOH1, PTF1α, PAX6, and KIRREL2, suggesting that this protocol generates glutamatergic and GABAergic cerebellar neuronal precursors, as well as Purkinje cell progenitors. Moreover, the differentiated cells show distinct neuronal morphology and are positive for immunofluorescence markers of neuronal identity such as TUBB3. These cells express axonal guidance molecules, including semaphorin-4C, plexin-B2, and neuropilin-1, and could serve as a model for investigating the molecular mechanisms of neurite outgrowth and synaptic connectivity. This method generates human cerebellar neurons useful for downstream applications, including gene expression, physiological, and morphological studies requiring 2D monolayer formats.

Thyroid hormone signaling in a human cellular model for early brain development

Thyroid hormone signaling in a human cellular model for early brain development

The role of type 3 deiodinase in a human model for early brain development

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Evaluation of the successful implementation of creative audio media models in early childhood education in Yogyakarta

The purpose of this study was to describe the successful application of audio media for the creation of early childhood development models in terms of reactions and aspects of the learning process. The method used is descriptive qualitative method implemented in Kindergarten Yogyakarta, Indonesia. The research subjects were determined using a purposive sampling technique where the research subjects were selected according to the research objectives. The research subjects include teachers and kindergarten students. Data was collected using direct observation/observation methods, and in-depth interview methods. The standard of data validity in qualitative research refers to the standards of credibility, transferability, dependability, and confirmability. The data analysis technique used is descriptive qualitative analysis with data reduction techniques, data presentation, and drawing conclusions. The conclusion of this research is the application of audio media for the creation of early childhood development models in terms of reactions and the learning process is suitable to be applied in early childhood schools, because it is interesting for students, makes the atmosphere fun, and creates joy in learning, students are very enthusiastic, students always active in practicing the steps according to the material presented in audio media.

An automated do-it-yourself system for dynamic stem cell and organoid culture in standard multi-well plates

SummaryWe present a low-cost, do-it-yourself system for complex mammalian cell culture under dynamically changing medium formulations by integrating conventional multi-well tissue culture plates with simple microfluidic control and system automation. We demonstrate the generation of complex concentration profiles, enabling the investigation of sophisticated input-response relations. We further apply our automated cell-culturing platform to the dynamic stimulation of two widely employed stem-cell-based in vitro models for early mammalian development: the conversion of naive mouse embryonic stem cells into epiblast-like cells and mouse 3D gastruloids. Performing automated medium-switch experiments, we systematically investigate cell fate commitment along the developmental trajectory toward mouse epiblast fate and examine symmetry-breaking, germ layer formation, and cardiac differentiation in mouse 3D gastruloids as a function of time-varying Wnt pathway activation. With these proof-of-principle examples, we demonstrate a highly versatile and scalable tool that can be adapted to specific research questions, experimental demands, and model systems.

L‐Citrulline Attenuates Effects of Serotonin Signalling During Proliferation of Pulmonary Artery Smooth Muscle Cells in Pulmonary Hypertension

IntroductionPremature infants are at risk for bronchopulmonary dysplasia (BPD), a disorder characterized by abnormal pulmonary development. Inflammation is one major component in causing BPD, which can further lead to abnormal vascular remodelling, causing pulmonary hypertension (PH). During this process, pulmonary artery smooth muscle cell (PASMC) proliferation and hypertrophy contribute to the thickening of the pulmonary artery wall, leading to heightened blood pressures. 5‐hydroxytryptamine (5‐HT) or serotonin has been implicated in PH and is involved in the pathogenesis of PH in adults. Meanwhile, L‐citrulline, a nitric oxide donor, has been effective in reducing PH in acute models of BPD. The role of 5‐HT signalling on PASMC proliferation during early pulmonary vascular development is currently unknown. Thus, the objective of this study is to establish the effect of 5‐HT on PASMC proliferation in a newborn model of early lung development, and to elucidate the interaction of 5‐HT on proliferation of PASMCs in the presence of LPS and L‐citrulline.MethodsSprague Dawley rat pups were grown and euthanized on postnatal day 4, after which the pulmonary arteries (PA) were isolated. Primary cultures of PASMCs were grown from PA explants and treated with varying concentrations of 5‐HT. Proliferation and cell viability assays were performed to measure growth and cell viability after exposure to 5‐HT and L‐citrulline (4mM). Lysate samples were also prepared with the cells to measure protein expression via Western blotting for Cyclin D1, an important protein involved in regulation of the cell cycle, and phosphorylated AKT (p‐AKT), which is involved in cell survival. To investigate the effects of inflammation on 5‐HT signalling, PASMCs were exposed to lipopolysaccharide (LPS, 3 µg/mL) and lysate samples were prepared to measure changes in the expression of the 5‐HT2A receptor.ResultsProliferation assays illustrated a dose‐dependent increase in growth of PASMCs exposed to 5‐HT, reaching a peak 150% growth rate (p < 0.05). Western blots revealed a three‐fold increase in Cyclin D1 expression (p < 0.01) and two‐fold increase in p‐AKT expression (p < 0.05) in PASMCs exposed to 5‐HT compared to protein expression of control PASMCs. Both changes were abrogated in PASMCs exposed to both L‐citrulline and 5‐HT, bringing expression of both proteins to control levels. When exposed to LPS, PASMCs have heightened expression of 5‐HT2A, reaching nearly two times higher than in control PASMCs. This effect is also reversed in PASMCs exposed to LPS and L‐citrulline (p < 0.05).ConclusionOur preliminary data support a role for 5‐HT in pathogenesis on BPD‐PH in the presence and absence of inflammation in a newborn model of lung development, and L‐citrulline may be an attractive safe therapeutic option to reverse or mitigate inflammation induced PH in a newborn model, which could later be translated to human infants.

Basketball jump shot technique design for high school athletes: Training method development

This study aims to improve the results of basketball jump shot training through a study of the development of training methods. The research method used is development research. Development research that refers to the development model of Borg and Gall, namely: 1) preliminary study, 2) early development model, 3) expert evaluation, 4) small-scale trial, 5) product revision, 6) group trial, 7) refine the model, 8) define the final model. Data are collected using a questionnaire obtained from the evaluation of basketball experts and coaches, then tested with a small group of 12 athletes and a large-scale trial of 24 athletes. The data are the results of an assessment of product quality, suggestions for product improvement, and the results of filling out questionnaires by athletes. The data analysis technique used is descriptive percentage to reveal the athlete's assessment after using the product. The results of the validation of the development of training methods from basketball experts obtain an average percentage of 94.5%. While the validation of the development of training methods from basketball coaches obtain an average percentage of 96.2%. The results of the questionnaire that is filled out by 12 athletes are 21.7% who answering difficult, 46.7% answering moderately, and 31.6% answering easy. The results of the analysis of small-scale trial data from 12 athletes obtain an average percentage of 20.83% answering difficult, 50% answering moderate, and 29.16% answering easy. The results of the analysis of large-scale trial data from 24 athletes obtain an average percentage of 6.7% who answering difficult, 19.1% answering moderately, and 74.1% answering easy. From the available data, it can be concluded that the development of the basketball jump shot training method can be used for basketball athletes from SMA Negeri 1 Majalengka.

Prognostic model of early inflammation development in periodontal tissues by biochemical parameters of oral fluid in patients with orthodontic appliances

One of the main etiological risk factors and pathogenetic mechanisms for the development of inflammatory diseases of the periodontal disease is a bite pathology or dentofacial anomalies. Therefore, in recent years, scientists make attempts to find new markers that would allow to predict the course of the disease at the preclinical stage of its diagnostics, which would allow to take preventive treatment. In recent years, individual proteins of the mouth, which include matrix metalloproteinases (MMP-8), which can hydrolyze the main proteins in extracellular space and lactoferrin, catelitsidine, KLOTHO protein should be considered leading markers. The purpose is to predict the emergence of early inflammation in periodontal tissues in patients with non-removable orthodontic appliance by studying protein content in the oral fluid in the dynamics of treatment. Among the 113 patients surveyed by us, which underwent orthodontic treatment with non-removable appliance, according to clinical and laboratory studies, 82 people (72,57%) had signs of early inflammation of periodontal tissues. All exa­mined young people were students or students of educational institutions who appealed for advice and treatment to a dental clinic. Biochemical studies of oral fluid and their analysis was conducted at the beginning of orthodontic treatment and 3 and 6 months after the delivery of non-removable orthodontic appliance. The oral fluid was collected in the morning, and the quantitative determination of proteins in it was carried out by the IFA method. In order to assess the probability of prognostication of early inflammation in patients with orthodontic appliance, there was made rank correlation analysis with the determination of the correlation coefficients of the disparity (rs), ROC analysis with the deter­mination of Optimal Cut-Off Point (OСР) – the value of the indicator for prediction and simple and multiple logistic regressions with the calculation of the odds ratio and the construction of a prognostic model (logistics regression equation). For the analysis of factors, on the basis of which it is possible to predict early inflammation of periodontal tissues in patients with orthodontic appliance, a correlation analysis was performed, which showed that the largest changes were in the biochemical parameters of the mouth, namely: MMP-8 (rs=0.58; p<0.001), lactoferin (rs=0.45; p<0.001), catelitsidine (rs= -0.59; p<0.001) and KLOTHO protein (rs= -0.58; p<0.001), with which statistically significant correlations were established. ROC analysis was used to evaluate the discriminatory capacity of the markers investigated, which showed the presence of statistically significant correlations with early signs of inflammatory process in periodontal tissues. As a result of the correlation analysis, it has been found that the most significant changes in the inflammatory process in periodontal tissues were in the biochemical parameters of the mouth, such as MMP-8 (rs=0.58; p< 0.001), lactoferin (rs=0.45; p< 0.001), catholicidine (rs= -0.59; p< 0.001) and Klotho protein (rs= -0.58; p< 0.001), with which statistically significant correlations of average force were detected. The chances of patients with non-removable orthodontic appliance for the development of inflammation in the periodontal tissues are increased by 4. times.

Dealbreakers, or dealbenders? Capturing the cumulative effects of partner information on mate choice

Entering and establishing a long-term relationship is typically a gradual process, as dating partners acquire information about each other over weeks or months. In contrast, existing mate selection paradigms (e.g., lab experiments, speed-dating) typically examine single brief encounters with real or potential mates. In the current research, we used a Choose Your Own Adventure design to examine how potential dealbreakers operate within the context of a broader relationship dynamic. In two studies, a combined total of 1585 participants read a story about a new dating relationship. At each of 17 junctures in the story, participants chose whether to continue dating or end the relationship. Potential dealbreakers were independently manipulated to be present or absent at each juncture, for a total of up to 17 negative pieces of information about the partner. Study 2 was a preregistered replication and extension of Study 1. On average, participants did not reject the hypothetical partner until several potential dealbreakers had been presented (M = 4.20 in Study 1, M = 3.68 in Study 2). Participants' self-reported dealbreakers consistently aligned with their in-story decisions. Even so, participants tended to encounter at least two of their own personal dealbreakers before choosing to reject (Study 2). Together, these studies highlight the sequential, iterative nature of partner evaluations, and illustrate a novel, accessible method for testing models of early relationship development.

Efficient embryoid-based method to improve generation of optic vesicles from human induced pluripotent stem cells.

Animal models have provided many insights into ocular development and disease, but they remain suboptimal for understanding human oculogenesis. Eye development requires spatiotemporal gene expression patterns and disease phenotypes can differ significantly between humans and animal models, with patient-associated mutations causing embryonic lethality reported in some animal models. The emergence of human induced pluripotent stem cell (hiPSC) technology has provided a new resource for dissecting the complex nature of early eye morphogenesis through the generation of three-dimensional (3D) cellular models. By using patient-specific hiPSCs to generate in vitro optic vesicle-like models, we can enhance the understanding of early developmental eye disorders and provide a pre-clinical platform for disease modelling and therapeutics testing. A major challenge of in vitro optic vesicle generation is the low efficiency of differentiation in 3D cultures. To address this, we adapted a previously published protocol of retinal organoid differentiation to improve embryoid body formation using a microwell plate. Established morphology, upregulated transcript levels of known early eye-field transcription factors and protein expression of standard retinal progenitor markers confirmed the optic vesicle/presumptive optic cup identity of in vitro models between day 20 and 50 of culture. This adapted protocol is relevant to researchers seeking a physiologically relevant model of early human ocular development and disease with a view to replacing animal models.

Predictive Statistical Model of Early Cranial Development.

We present a data-driven method to build a spatiotemporal statistical shape model predictive of normal cranial growth from birth to the age of 2 years. The model was constructed using a normative cross-sectional computed tomography image dataset of 278 subjects. First, we propose a new standard representation of the calvaria using spherical maps to establish anatomical correspondences between subjects at the cranial sutures - the main areas of cranial bone expansion. Then, we model the cranial bone shape as a bilinear function of two factors: inter-subject anatomical variability and temporal growth. We estimate these factors using principal component analysis on the spatial and temporal dimensions, using a novel coarse-to-fine temporal multi-resolution approach to mitigate the lack of longitudinal images of the same patient. Our model achieved an accuracy of 1.54 ± 1.05 mm predicting development on an independent longitudinal dataset. We also used the model to calculate the cranial volume, cephalic index and cranial bone surface changes during the first two years of age, which were in agreement with clinical observations. To our knowledge, this is the first data-driven and personalized predictive model of cranial bone shape development during infancy and it can serve as a baseline to study abnormal growth patterns in the population.

Can we do that here? An analysis of US federal and state policies guiding human embryo and embryoid research.

Recent technological advances have helped scientists understand early human development. However, scientists’ ability to fully explore their potential comes in conflict with national and state-level policies in the USA. In 2016, for the first time, researchers were able to grow human embryos in culture up to 14 days but stopped because of scientific and legal limits. Other researchers have used stem cells in culture to create organized models of early human development, known as embryoids or cell-based embryo models. In this paper, we review federal and state laws that affect US human embryo and embryoid research. While federal policies focus on funding, state laws are often associated with human embryonic stem cells, abortion, fetal tissue research, and reproductive cloning. Of the 29 states with laws impacting human embryo research, only 11 states ban it, and none address embryoids directly, although five states limit aspects of this research. Overall, this complicated landscape suggests that additional national guidance would help scientists and the public navigate these controversial areas of research, however, it is unlikely to happen, considering the lack of past progress determining embryo research policy.

Persons in the Making: Perceptions of the Beginning of Life in a Zambian Community

AbstractInfancy is characterized by physical and biological changes and growth, and across cultures, parents associate this period with care, protection, and nutrition. However, beyond the universal aspects of infancy, the ways in which caretakers understand babies’ needs and nature are subject to great cultural variation. In this article I explore how people in a township in Lusaka, Zambia, conceptualize and understand how babies become social persons. Particular attention is paid to how human potentials are seen to naturally grow and unfold if properly cultivated in the relationships that the child shares with others. I will also discuss how local models of natural growth contrast models of early child development offered by international parenting intervention programs that focus on how parents in poor communities can stimulate young children's cognitive development.

Toxicity of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in early development: A wide-scope metabolomics assay in zebrafish embryos

The tobacco-specific nitrosamine 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a carcinogenic and ubiquitous environmental pollutant for which toxic activity has been thoroughly investigated in murine models and human tissues. However, its potential deleterious effects on vertebrate early development are yet poorly understood. In this work, we characterized the impact of NNK exposure during early developmental stages of zebrafish embryos, a known alternative model for mammalian toxicity studies. Embryos exposed to different NNK concentrations were monitored for lethality and for the appearance of malformations during the first five days after fertilization. LC-MS based untargeted metabolomics was subsequently performed for a wide-scope assay of NNK-related metabolic alterations. Our results revealed the presence of not only the parental compound, but also of two known NNK metabolites, 4-Hydroxy-4-(3-pyridyl)-butyric acid (HPBA) and 4-(Methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanol (NNAL-N-oxide) in exposed embryos likely resulting from active CYP450-mediated α-hydroxylation and NNK detoxification pathways, respectively. This was paralleled by a disruption in purine and pyrimidine metabolisms and the activation of the base excision repair pathway. Our results confirm NNK as a harmful embryonic agent and demonstrate zebrafish embryos to be a suitable early development model to monitor NNK toxicity.

'Consciousnessoids': clues and insights from human cerebral organoids for the study of consciousness.

Human cerebral organoids (HCOs) are an in vitro three-dimensional model of early neural development, aimed at modelling and understanding brain development and neurological disorders. In just a few years, there has been a rapid and considerable progress in the attempt to create a brain model capable of showcasing the structure and functions of the human brain. There are still strong limitations to address, including the absence of vascularization that makes it difficult to feed the central layers of organoids. Nevertheless, some important features of the nervous system have recently been observed: HCOs manifest electrical activity, are sensitive to light stimulation and are able to connect to a spinal cord by sending impulses that make a muscle contract. Recent data show that cortical organoid network development at 10 months resembles some preterm babies’ electroencephalography (EEG) patterns. In the light of the fast pace of research in this field, one might consider the hypothesis that HCOs might become a living laboratory for studying the emergence of consciousness and investigating its mechanisms and neural correlates. HCOs could be also a benchmark for different neuroscientific theories of consciousness. In this paper, I propose some potential lines of research and offer some clues and insights so as to use HCOs in trying to unveil some puzzles concerning our conscious states. Finally, I consider some relevant ethical issues regarding this specific experimentation on HCOs and conclude that some of them could require strict regulation in this field.

Human Embryos, Induced Pluripotent Stem Cells, and Organoids: Models to Assess the Effects of Environmental Plastic Pollution.

For a long time, animal models were used to mimic human biology and diseases. However, animal models are not an ideal solution due to numerous interspecies differences between humans and animals. New technologies, such as human-induced pluripotent stem cells and three-dimensional (3D) cultures such as organoids, represent promising solutions for replacing, refining, and reducing animal models. The capacity of organoids to differentiate, self-organize, and form specific, complex, biologically suitable structures makes them excellent in vitro models of development and disease pathogenesis, as well as drug-screening platforms. Despite significant potential health advantages, further studies and considerable nuances are necessary before their clinical use. This article summarizes the definition of embryoids, gastruloids, and organoids and clarifies their appliance as models for early development, diseases, environmental pollution, drug screening, and bioinformatics.