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Cold Spring Harbor Perspectives in... Oct 2020Early heart morphogenesis involves a process in which embryonic precursor cells are instructed to form a cyclic contracting muscle tube connected to blood vessels,... (Review)
Review
Early heart morphogenesis involves a process in which embryonic precursor cells are instructed to form a cyclic contracting muscle tube connected to blood vessels, pumping fluid. Subsequently, the heart becomes structurally complex and its size increases several orders of magnitude to functionally keep up with the demands of the growing organism. Programmed transcriptional regulatory networks control the early steps of cardiac development. However, already during the early stages of its assembly, the heart tube starts to produce electrochemical potentials, contractions, and flow, which are transduced into signals that feed back into the process of morphogenesis itself. Heart morphogenesis, thus, involves the interplay between progressively changing genetic networks, function, and shape. Morphogenesis is evolutionarily conserved, but species-specific differences occur and in mouse, for instance, distinct phases of development become overlapping and compounded in an extremely fast gestation. Here, we review the early morphogenesis of the chambered heart that maintains a circulation supporting development of an organism rapidly growing in size and requirements.
Topics: Animals; Embryonic Development; Gene Expression Regulation, Developmental; Heart; Humans; Myocardium; Organogenesis
PubMed: 31932321
DOI: 10.1101/cshperspect.a037143 -
Development (Cambridge, England) May 2010Many genes and molecules that drive tissue patterning during organogenesis and tissue regeneration have been discovered. Yet, we still lack a full understanding of how... (Review)
Review
Many genes and molecules that drive tissue patterning during organogenesis and tissue regeneration have been discovered. Yet, we still lack a full understanding of how these chemical cues induce the formation of living tissues with their unique shapes and material properties. Here, we review work based on the convergence of physics, engineering and biology that suggests that mechanical forces generated by living cells are as crucial as genes and chemical signals for the control of embryological development, morphogenesis and tissue patterning.
Topics: Animals; Biomechanical Phenomena; Embryonic Development; Humans; Models, Biological; Morphogenesis; Organogenesis; Signal Transduction
PubMed: 20388652
DOI: 10.1242/dev.024166 -
Ptf1a function and transcriptional cis-regulation, a cornerstone in vertebrate pancreas development.The FEBS Journal Sep 2022Vertebrate pancreas organogenesis is a stepwise process regulated by a complex network of signaling and transcriptional events, progressively steering the early endoderm... (Review)
Review
Vertebrate pancreas organogenesis is a stepwise process regulated by a complex network of signaling and transcriptional events, progressively steering the early endoderm toward pancreatic fate. Many crucial players of this process have been identified, including signaling pathways, cis-regulatory elements, and transcription factors (TFs). Pancreas-associated transcription factor 1a (PTF1A) is one such TF, crucial for pancreas development. PTF1A mutations result in dramatic pancreatic phenotypes associated with severe complications, such as neonatal diabetes and impaired food digestion due to exocrine pancreatic insufficiency. Here, we present a brief overview of vertebrate pancreas development, centered on Ptf1a function and transcriptional regulation, covering similarities and divergences in three broadly studied organisms: human, mouse and zebrafish.
Topics: Animals; Gene Expression Regulation, Developmental; Humans; Mice; Organogenesis; Pancreas; Transcription Factors; Zebrafish
PubMed: 34125483
DOI: 10.1111/febs.16075 -
Biophysical Journal Sep 2023Organogenesis arises from the collective arrangement of cells into progressively 3D-shaped tissue. The acquisition of a correctly shaped organ is then the result of a... (Review)
Review
Organogenesis arises from the collective arrangement of cells into progressively 3D-shaped tissue. The acquisition of a correctly shaped organ is then the result of a complex interplay between molecular cues, responsible for differentiation and patterning, and the mechanical properties of the system, which generate the necessary forces that drive correct shape emergence. Nowadays, technological advances in the fields of microscopy, molecular biology, and computer science are making it possible to see and record such complex interactions in incredible, unforeseen detail within the global context of the developing embryo. A quantitative and interdisciplinary perspective of developmental biology becomes then necessary for a comprehensive understanding of morphogenesis. Here, we provide a roadmap to quantify the events that lead to morphogenesis from imaging to image analysis, quantification, and modeling, focusing on the discrete cellular and tissue shape changes, as well as their mechanical properties.
Topics: Biomechanical Phenomena; Morphogenesis; Organogenesis; Cytoskeleton; Cell Differentiation
PubMed: 37243338
DOI: 10.1016/j.bpj.2023.05.015 -
Developmental Cell Sep 2016Organoids are three-dimensional in-vitro-grown cell clusters with near-native microanatomy that arise from self-organizing mammalian pluripotent or adult stem cells.... (Review)
Review
Organoids are three-dimensional in-vitro-grown cell clusters with near-native microanatomy that arise from self-organizing mammalian pluripotent or adult stem cells. Although monolayer stem cell cultures were established more than 40 years ago, organoid technology has recently emerged as an essential tool for both fundamental and biomedical research. For developmental biologists, organoids provide powerful means for ex vivo modeling of tissue morphogenesis and organogenesis. Here we discuss how organoid cultures of the intestine and other tissues have been established and how they are utilized as an in vitro model system for stem cell research and developmental biology.
Topics: Cell Culture Techniques; Humans; Intestines; Models, Biological; Morphogenesis; Organogenesis; Organoids; Pluripotent Stem Cells; Stem Cell Niche
PubMed: 27676432
DOI: 10.1016/j.devcel.2016.08.014 -
Trends in Endocrinology and Metabolism:... Aug 2014Developing cell-based diabetes therapies requires examining transcriptional mechanisms underlying human β cell development. However, increased knowledge is hampered by... (Review)
Review
Developing cell-based diabetes therapies requires examining transcriptional mechanisms underlying human β cell development. However, increased knowledge is hampered by low availability of fetal pancreatic tissue and gene targeting strategies. Rodent models have elucidated transcription factor roles during islet organogenesis and maturation, but differences between mouse and human islets have been identified. The past 5 years have seen strides toward generating human β cell lines, the examination of human transcription factor expression, and studies utilizing induced pluripotent stem cells (iPS cells) and human embryonic stem (hES) cells to generate β-like cells. Nevertheless, much remains to be resolved. We present current knowledge of developing human β cell transcription factor expression, as compared to rodents. We also discuss recent studies employing transcription factor or epigenetic modulation to generate β cells.
Topics: Humans; Insulin-Secreting Cells; Islets of Langerhans; Organogenesis; Transcription Factors
PubMed: 24831984
DOI: 10.1016/j.tem.2014.03.013 -
Advances in Cancer Research 2015The inflammatory status of the tumor microenvironment (TME) has been heavily investigated in recent years. Chemokine- and cytokine-signaling pathways such as CCR7,... (Review)
Review
The inflammatory status of the tumor microenvironment (TME) has been heavily investigated in recent years. Chemokine- and cytokine-signaling pathways such as CCR7, CXCR5, lymphotoxin, and IL-36, which are involved in the generation of secondary lymphoid organs and effector immune responses, are now recognized as having value both as prognostic factors and as immunomodulatory therapeutics in the context of cancer. Furthermore, when produced in the TME, these mediators have been shown to promote the recruitment of immune cells, including T cells, B cells, dendritic cells (DCs), and other specialized immune cell subsets such as follicular DCs and T follicular helper cells, in association with the formation of "tertiary" lymphoid structures (TLSs) within or adjacent to sites of disease. Although TLSs are composed of a heterogeneous collection of immune cell types, whose composition differs based on cancer subtype, the qualitative presence of TLSs has been shown to represent a biomarker of good prognosis for cancer patients. A comprehensive understanding of the role each of these pathways plays within the TME may support the rational design of future immunotherapies to selectively promote/bolster TLS formation and function, leading to improved clinical outcomes across the vast range of solid cancer types.
Topics: Animals; Humans; Lymphoid Tissue; Neoplasms; Organogenesis; Tumor Microenvironment
PubMed: 26216634
DOI: 10.1016/bs.acr.2015.04.003 -
Development (Cambridge, England) Apr 2019Organoids are complex three-dimensional organ-like model systems. Human organoids, which are derived from human pluripotent stem cells or primary human donor tissue,... (Review)
Review
Organoids are complex three-dimensional organ-like model systems. Human organoids, which are derived from human pluripotent stem cells or primary human donor tissue, have been used to address fundamental questions about human development, stem cell biology and organ regeneration. Focus has now shifted towards implementation of organoids for biological discovery and advancing existing systems to more faithfully recapitulate the native organ. This work has highlighted significant unknowns in human biology and has invigorated new exploration into the cellular makeup of human organs during development and in the adult - work that is crucial for providing appropriate benchmarks for organoid systems. In this Review, we discuss efforts to characterize human organ cellular complexity and attempts to make organoid models more realistic through co-culture, transplantation and bioengineering approaches.
Topics: Animals; Bioengineering; Coculture Techniques; Humans; Models, Biological; Organogenesis; Organoids
PubMed: 30992275
DOI: 10.1242/dev.166173 -
Current Opinion in Genetics &... Oct 2022The vertebrate inner ear contains a diversity of unique cell types arranged in a particularly complex 3D cytoarchitecture. Both of these features are integral to the... (Review)
Review
The vertebrate inner ear contains a diversity of unique cell types arranged in a particularly complex 3D cytoarchitecture. Both of these features are integral to the proper development, function, and maintenance of hearing and balance. Since the elucidation of the timing and delivery of signaling molecules to produce inner ear sensory cells, supporting cells, and neurons from human induced pluripotent stem cells, we have entered a revolution using organ-like 'otic organoid' cultures to explore inner ear specific genetic programs, developmental rules, and potential therapeutics. This review aims to highlight a selection of reviews and primary research papers from the past two years of particular merit that use otic organoids to investigate the broadly defined topics of cell reprogramming, regeneration, and repair.
Topics: Cell Differentiation; Ear, Inner; Humans; Induced Pluripotent Stem Cells; Organogenesis; Organoids
PubMed: 35853286
DOI: 10.1016/j.gde.2022.101954 -
Seminars in Cell & Developmental Biology Oct 2021Organoids, or miniaturized organs formed in vitro, hold potential to revolutionize how researchers approach and answer fundamental biological and pathological questions.... (Review)
Review
Organoids, or miniaturized organs formed in vitro, hold potential to revolutionize how researchers approach and answer fundamental biological and pathological questions. In the context of cardiac biology, development of a bona fide cardiac organoid enables study of heart development, function, and pathogenesis in a dish, providing insight into the nature of congenital heart disease and offering the opportunity for high-throughput probing of adult heart disease and drug discovery. Recently, multiple groups have reported novel methods for generating in vitro models of the heart; however, there are substantial conceptual and methodological differences. In this review we will evaluate recent cardiac organoid studies through the lens of the core principles of organoid technology: patterned self-organization of multiple cell types resembling the in vivo organ. Based on this, we will classify systems into the following related types of tissues: developmental cardiac organoids, chamber cardiac organoids, microtissues, and engineered heart tissues. Furthermore, we highlight the interventions which allow for organoid formation, such as modulation of highly conserved cardiogenic signaling pathways mediated by developmental morphogens. We expect that consolidation and categorization of existing organoid models will help eliminate confusion in the field and facilitate progress towards creation of an ideal cardiac organoid.
Topics: Heart; Humans; Organogenesis; Organoids
PubMed: 33775518
DOI: 10.1016/j.semcdb.2021.03.011