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Endocrine Journal May 2017A small number of cells in the adult pancreas are endocrine cells. They are arranged in clusters called islets of Langerhans. The islets make insulin, glucagon, and... (Review)
Review
A small number of cells in the adult pancreas are endocrine cells. They are arranged in clusters called islets of Langerhans. The islets make insulin, glucagon, and other endocrine hormones, and release them into the blood circulation. These hormones help control the level of blood glucose. Therefore, a dysfunction of endocrine cells in the pancreas results in impaired glucose homeostasis, or diabetes mellitus. The pancreas is an organ that originates from the evaginations of pancreatic progenitor cells in the epithelium of the foregut endoderm. Pancreas organogenesis and maturation of the islets of Langerhans occurs via a coordinated and complex interplay of transcriptional networks and signaling molecules, which guide a stepwise and repetitive process of the propagation of progenitor cells and their maturation, eventually resulting in a fully functional organ. Increasing our understanding of the extrinsic, as well as intrinsic mechanisms that control these processes should facilitate the efforts to generate surrogate β cells from ES or iPS cells, or to reactivate the function of important cell types within pancreatic islets that are lost in diabetes.
Topics: Animals; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Humans; Insulin-Secreting Cells; Organogenesis; Pancreas; Transcription, Genetic
PubMed: 28420858
DOI: 10.1507/endocrj.EJ17-0098 -
Cellular and Molecular Life Sciences :... Nov 2006Perlecan is a large multi-domain extracellular matrix proteoglycan that plays a crucial role in tissue development and organogenesis. In vertebrates, perlecan functions... (Review)
Review
Perlecan is a large multi-domain extracellular matrix proteoglycan that plays a crucial role in tissue development and organogenesis. In vertebrates, perlecan functions in a diverse range of developmental and biological processes, from the establishment of cartilage to the regulation of wound healing. How can a single molecule modulate such a wide variety of processes? We suggest that perlecan employs the same basic mechanism, based on interactions with growth factors, morphogens and matrix proteins, to regulate each of these processes and that the local extracellular environment determines the function of perlecan and consequently its downstream effects on the structure and function of the organ. We discuss this hypothesis in relation to its role in three major vertebrate developmental processes: angiogenesis, chondrogenesis and endochondral ossification.
Topics: Animals; Blood Vessels; Chondrogenesis; Heparan Sulfate Proteoglycans; Humans; Neovascularization, Physiologic; Osteogenesis
PubMed: 16952056
DOI: 10.1007/s00018-006-6162-z -
The International Journal of... 2018This brief review considers the question of why some animals can regenerate and others cannot and elaborates the opposing views that have been expressed in the past on... (Review)
Review
This brief review considers the question of why some animals can regenerate and others cannot and elaborates the opposing views that have been expressed in the past on this topic, namely that regeneration is adaptive and has been gained or that it is a fundamental property of all organisms and has been lost. There is little empirical evidence to support either view, but some of the best comes from recent phylogenetic analyses of regenerative ability in Planarians which reveals that this property has been lost and gained several times in this group. In addition, a non-regenerating species has been induced to regenerate by altering only one signaling pathway. Extrapolating this to mammals it may be the case that there is more regenerative ability in mammals than has typically been thought to exist and that inducing regeneration in humans may not be as impossible as it may seem. The regenerative abilities of mammals is described and it turns out that there are several examples of classical epimorphic regeneration involving a blastema as exemplified by the regenerating Urodele limb that can be seen in mammals. Even the heart can regenerate in mammals which has long been considered to be a property unique to Urodeles and fish and several recent examples of regeneration have come from recent studies of the spiny mouse, Acomys, which are discussed here. It is suggested that a much more thorough phylogenetic analysis of mammalian regeneration would likely reveal some important insights into the evolution of regeneration.
Topics: Animals; Biological Evolution; Extremities; Humans; Mammals; Organogenesis; Phylogeny; Planarians; Regeneration
PubMed: 29938749
DOI: 10.1387/ijdb.180031mm -
Developmental Dynamics : An Official... Sep 2021
Topics: Extremities; Organogenesis; Regeneration
PubMed: 34402127
DOI: 10.1002/dvdy.411 -
Development (Cambridge, England) Feb 2014With the high prevalence of gastrointestinal disorders, there is great interest in establishing in vitro models of human intestinal disease and in developing... (Review)
Review
With the high prevalence of gastrointestinal disorders, there is great interest in establishing in vitro models of human intestinal disease and in developing drug-screening platforms that more accurately represent the complex physiology of the intestine. We will review how recent advances in developmental and stem cell biology have made it possible to generate complex, three-dimensional, human intestinal tissues in vitro through directed differentiation of human pluripotent stem cells. These are currently being used to study human development, genetic forms of disease, intestinal pathogens, metabolic disease and cancer.
Topics: Cell Differentiation; Humans; Intestines; Models, Biological; Organ Culture Techniques; Organogenesis; Pluripotent Stem Cells; Tissue Engineering
PubMed: 24496613
DOI: 10.1242/dev.097386 -
Developmental Biology Jul 2012During organogenesis, tissues expand in size and eventually acquire consistent ratios of cells with dazzling diversity in morphology and function. During this process... (Review)
Review
During organogenesis, tissues expand in size and eventually acquire consistent ratios of cells with dazzling diversity in morphology and function. During this process progenitor cells exit the cell cycle and execute differentiation programs through extensive genetic reprogramming that involves the silencing of proliferation genes and the activation of differentiation genes in a step-wise temporal manner. Recent years have witnessed expansion in our understanding of the epigenetic mechanisms that contribute to cellular differentiation and maturation during organ development, as this is a crucial step toward advancing regenerative therapy research for many intractable disorders. Among such epigenetic programs, the developmental roles of the polycomb repressive complex 2 (PRC2), a chromatin remodeling complex that mediates silencing of gene expression, have been under intensive examination. This review summarizes recent findings of how PRC2 functions to regulate the transition from proliferation to differentiation during organogenesis and discusses some aspects of the remaining questions associated with its regulation and mechanisms of action.
Topics: Animals; Cell Differentiation; Cell Lineage; Chromatin Assembly and Disassembly; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Humans; Muscle Development; Neurogenesis; Organogenesis; Polycomb-Group Proteins; Protein Processing, Post-Translational; Repressor Proteins
PubMed: 22565092
DOI: 10.1016/j.ydbio.2012.04.030 -
Journal of Biochemistry Jun 2016Statistical analyses based on the quantitative data from real multicellular organisms are useful as inductive-type studies to analyse complex morphogenetic events in... (Review)
Review
Statistical analyses based on the quantitative data from real multicellular organisms are useful as inductive-type studies to analyse complex morphogenetic events in addition to deductive-type analyses using mathematical models. Here, we introduce several of our trials for the statistical analysis of organogenesis and histogenesis of human and mouse embryos and foetuses. Multidimensional scaling has been applied to prove the existence and examine the mode of interkinetic nuclear migration, a regulatory mechanism of stem cell proliferation/differentiation in epithelial tubular tissues. Several statistical methods were used on morphometric data from human foetuses to establish the multidimensional standard growth curve and to describe the relation among the developing organs and body parts. Although the results are still limited, we show that these analyses are not only useful to understand the normal and abnormal morphogenesis in humans and mice but also to provide clues that could correlate aspects of prenatal developmental events with postnatal diseases.
Topics: Animals; Embryo, Mammalian; Humans; Mice; Organogenesis
PubMed: 26935132
DOI: 10.1093/jb/mvw020 -
Current Topics in Developmental Biology 2016The basic unit of kidney function is the nephron. In the mouse, around 14,000 nephrons form in a 10-day period extending into early neonatal life, while the human fetus... (Review)
Review
The basic unit of kidney function is the nephron. In the mouse, around 14,000 nephrons form in a 10-day period extending into early neonatal life, while the human fetus forms the adult complement of nephrons in a 32-week period completed prior to birth. This review discusses our current understanding of mammalian nephrogenesis: the contributing cell types and the regulatory processes at play. A conceptual developmental framework has emerged for the mouse kidney. This framework is now guiding studies of human kidney development enabled in part by in vitro systems of pluripotent stem cell-seeded nephrogenesis. A near future goal will be to translate our developmental knowledge-base to the productive engineering of new kidney structures for regenerative medicine.
Topics: Adult; Animals; Cell Differentiation; Humans; Kidney; Mice; Nephrons; Organogenesis; Regenerative Medicine
PubMed: 26969971
DOI: 10.1016/bs.ctdb.2015.10.010 -
Stem Cell Reviews and Reports Apr 2022One of the most exciting advances in life science research is the development of 3D cell culture systems to obtain complex structures called organoids and spheroids.... (Review)
Review
One of the most exciting advances in life science research is the development of 3D cell culture systems to obtain complex structures called organoids and spheroids. These 3D cultures closely mimic in vivo conditions, where cells can grow and interact with their surroundings. This allows us to better study the spatio-temporal dynamics of organogenesis and organ function. Furthermore, physiologically relevant organoids cultures can be used for basic research, medical research, and drug discovery. Although most of the research thus far focuses on the development of heart, liver, kidney, and brain organoids, to name a few, most recently, these structures were obtained using dental stem cells to study in vitro tooth regeneration. This review aims to present the most up-to-date research showing how dental stem cells can be grown on specific biomaterials to induce their differentiation in 3D. The possibility of combining engineering and biology principles to replicate and/or increase tissue function has been an emerging and exciting field in medicine. The use of this methodology in dentistry has already yielded many interesting results paving the way for the improvement of dental care and successful therapies.
Topics: Biocompatible Materials; Dentistry; Organogenesis; Organoids; Stem Cells
PubMed: 35015212
DOI: 10.1007/s12015-021-10326-4 -
Genome Biology Sep 2022Perturbation of DNA methyltransferases (DNMTs) and of the active DNA demethylation pathway via ten-eleven translocation (TET) methylcytosine dioxygenases results in...
BACKGROUND
Perturbation of DNA methyltransferases (DNMTs) and of the active DNA demethylation pathway via ten-eleven translocation (TET) methylcytosine dioxygenases results in severe developmental defects and embryonic lethality. Dynamic control of DNA methylation is therefore vital for embryogenesis, yet the underlying mechanisms remain poorly understood.
RESULTS
Here we report a single-cell transcriptomic atlas from Dnmt and Tet mutant mouse embryos during early organogenesis. We show that both the maintenance and de novo methyltransferase enzymes are dispensable for the formation of all major cell types at E8.5. However, DNA methyltransferases are required for silencing of prior or alternative cell fates such as pluripotency and extraembryonic programmes. Deletion of all three TET enzymes produces substantial lineage biases, in particular, a failure to generate primitive erythrocytes. Single-cell multi-omics profiling moreover reveals that this is linked to a failure to demethylate distal regulatory elements in Tet triple-knockout embryos.
CONCLUSIONS
This study provides a detailed analysis of the effects of perturbing DNA methylation on mouse organogenesis at a whole organism scale and affords new insights into the regulatory mechanisms of cell fate decisions.
Topics: Animals; DNA; DNA Methylation; Dioxygenases; Methyltransferases; Mice; Organogenesis
PubMed: 36163261
DOI: 10.1186/s13059-022-02762-3