scholarly journals Modeling lung cell development using human pluripotent stem cells

2021 ◽  
Author(s):  
Zoe Ngan ◽  
Henry Quach ◽  
Joshua Dierolf ◽  
Jin-A Lee ◽  
Elena Nicole Huang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Lung Development ◽  
Disease Modeling ◽  
Developmental Trajectories ◽  
Cell Lineage ◽  
Fetal Lung ◽  
Cell Types ◽  
Cell Lineages ◽  
Lung Progenitor ◽  
Air Liquid Interface

Human PSC (hPSC) differentiations can capture developmental phenotypes and processes and are useful for studying fundamental biological mechanisms driving tissue morphogenesis and cell lineage development. Here, we show for the first time the temporal development of lung cell lineages using hPSC that model developmental milestones observed in primary tissue, the generation of renewable fetal lung epithelial organoids, and the functional utility of the lung models at different differentiation stages for Cystic fibrosis disease modeling. We first show the presence of hPSC-derived lung progenitor cells reminiscent of early trimester lung development and can capture a population enriched with basal stem cells that generates renewable airway organoids. Maturation and polarization in air liquid interface (ALI) generates additional epithelial cell lineages found in adult lung tissues including pulmonary neuroendocrine, brush, mature basal, ciliated and secretory cell types. Finally, pseudotime analysis of the integrated datasets from the fetal and ALI stages reveal the developmental trajectories of the cells as they emerge during differentiation. Overall, hPSC differentiation can capture aspects of human lung development and potentially provide important insight into congenital causes of diseases.

scholarly journals Modeling lung cell development using human pluripotent stem cells

2021 ◽  
Author(s):  
Amy Wong
Keyword(s):  
Stem Cells ◽  
Lung Development ◽  
Disease Modeling ◽  
Cell Lineage ◽  
Fetal Lung ◽  
Cell Types ◽  
Cell Lineages ◽  
Lung Progenitor ◽  
Air Liquid Interface ◽  
First Time

Abstract Human PSC (hPSC) differentiations can capture developmental phenotypes and processes and are useful for studying fundamental biological mechanisms driving tissue morphogenesis and cell lineage development. Here, we show for the first time the temporal development of lung cell lineages using hPSC that model developmental milestones observed in primary tissue, the generation of renewable fetal lung epithelial spheroids, and the functional utility of the lung models at different differentiation stages for Cystic fibrosis disease modeling. We first show the presence of hPSC-derived lung progenitor cells reminiscent of early trimester lung development and containing basal stem cells that generate renewable airway spheroids. Maturation and polarization in air liquid interface (ALI) generates additional epithelial cell lineages found in adult airways including pulmonary neuroendocrine, brush, mature basal, ciliated and secretory cell types. Finally, pseudotime and RNA velocity analyses of the integrated datasets from the fetal and ALI stages reveal previously identified and new cell lineage relationships. Overall, hPSC differentiation can capture aspects of human lung development and potentially provide important insight into congenital causes of diseases.

scholarly journals A Gene Network Model for Developing Cell Lineages

2005 ◽  
Vol 11 (3) ◽  
pp. 249-267 ◽  
Author(s):  
Nicholas Geard ◽  
Janet Wiles
Keyword(s):  
Gene Network ◽  
Temporal Dynamics ◽  
Developmental Trajectories ◽  
Cell Lineage ◽  
Cell Types ◽  
External Input ◽  
Sufficient Information ◽  
Cell Lineages ◽  
C Elegans ◽  
Task Definition

Biological development is a remarkably complex process. A single cell, in an appropriate environment, contains sufficient information to generate a variety of differentiated cell types, whose spatial and temporal dynamics interact to form detailed morphological patterns. While several different physical and chemical processes play an important role in the development of an organism, the locus of control is the cell's gene regulatory network. We designed a dynamic recurrent gene network (DRGN) model and evaluated its ability to control the developmental trajectories of cells during embryogenesis. Three tasks were developed to evaluate the model, inspired by cell lineage specification in C. elegans, describing the variation in gene activity required for early cell diversification, combinatorial control of cell lineages, and cell lineage termination. Three corresponding sets of simulations compared performance on the tasks for different gene network sizes, demonstrating the ability of DRGNs to perform the tasks with minimal external input. The model and task definition represent a new means of linking the fundamental properties of genetic networks with the topology of the cell lineages whose development they control.

scholarly journals Aspects of the biology of regeneration and repair in the human gastrointestinal tract

1998 ◽  
Vol 353 (1370) ◽  
pp. 925-933 ◽  
Author(s):  
Nicholas A. Wright
Keyword(s):  
Stem Cells ◽  
Gastric Gland ◽  
Cell Lineage ◽  
Mucosal Ulceration ◽  
Cell Lineages ◽  
Trefoil Peptides ◽  
Pyloric Mucosa ◽  
A Cell ◽  
Epidermal Growth ◽  
Altered Gene

The main pathways of epithelial differentiation in the intestine, Paneth, mucous, endocrine and columnar cell lineages are well recognized. However, in abnormal circumstances, for example in mucosal ulceration, a cell lineage with features distinct from these emerges, which has often been dismissed in the past as ‘pyloric’ metaplasia, because of its morphological resemblance to the pyloric mucosa in the stomach. However, we can conclude that this cell lineage has a defined phenotype unique in gastrointestinal epithelia, has a histogenesis that resembles that of Brunner's glands, but acquires a proliferative organization similar to that of the gastric gland. It expresses several peptides of particular interest, including epidermal growth factor, the trefoil peptides TFF1, TFF2, TFF3, lysozyme and PSTI. The presence of this lineage also appears to cause altered gene expression in adjacent indigenous cell lineages. We propose that this cell lineage is induced in gastrointestinal stem cells as a result of chronic mucosal ulceration, and plays an important part in ulcer healing; it should therefore be added to the repertoire of gastrointestinal stem cells.

scholarly journals From blastocyst to gastrula: gene regulatory networks of embryonic stem cells and early mouse embryogenesis

2014 ◽  
Vol 369 (1657) ◽  
pp. 20130542 ◽  
Author(s):  
David-Emlyn Parfitt ◽  
Michael M. Shen
Keyword(s):  
Stem Cells ◽  
Gene Networks ◽  
Regulatory Networks ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Network Models ◽  
Cell Types ◽  
Mammalian Development ◽  
A Genome

To date, many regulatory genes and signalling events coordinating mammalian development from blastocyst to gastrulation stages have been identified by mutational analyses and reverse-genetic approaches, typically on a gene-by-gene basis. More recent studies have applied bioinformatic approaches to generate regulatory network models of gene interactions on a genome-wide scale. Such models have provided insights into the gene networks regulating pluripotency in embryonic and epiblast stem cells, as well as cell-lineage determination in vivo . Here, we review how regulatory networks constructed for different stem cell types relate to corresponding networks in vivo and provide insights into understanding the molecular regulation of the blastocyst–gastrula transition.

Stem Cells Applications in Therapeutics and Site-Specific Genome Editing Through CRISPR Cas9 System

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Javed M ◽  
◽  
Khan A ◽  
Mukheed M ◽  
◽  
...  
Keyword(s):  
Stem Cells ◽  
Genome Editing ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Cell Types ◽  
Multipotent Stem Cells ◽  
Site Specific ◽  
Regenerative Medicines ◽  
Induced Pluripotent ◽  
Adult Cells

Stem cells ae immature cells that have ability to differentiate into all specific and mature cells in body. The two main characteristics of stem cells are selfrenewable and ability to differentiate into all mature, functional and adult cells types. There are the two major classes a) pluripotent stem cells which have potential to differentiate in all adult cell and b) multipotent stem cells which have capacity to differentiate into many adult cells but not in all cell types. Due to the self-renewable ability stem cells are use in therapeutics, tissue regeneration, disease modeling and regenerative medicines and to treat cardiovascular diseases, neural disorders such as Parkinson’s disease and most importantly to treat carcinomas. The human induced pluripotent stem cells provide a great platform to study and treatment of human diseases because these are able to differentiate into many functional and specialized adult cells of body. The genome editing tools such as CRISPR Cas9 system and TALENs are used to generate multiple DNA variants in hPSCs by inducing site specific mutations, frame shift mutation and deletion. In present days CRISPR Cas9 is more efficient and frequent method for genome editing which is derived from bacterial cell.

Investigation of the Stem Cells Used in Modeling Human Placental Trophoblast

2021 ◽  
Author(s):  
Lulu Ji ◽  
Lin Wang
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Cell Types ◽  
Model Systems ◽  
Alternative Methods ◽  
Laboratory Animals ◽  
Placental Development ◽  
Induced Pluripotent

Human placenta is vital for fetal development, and act as an interface between the fetus and the expecting mother. Abnormal placentati on underpins various pregnancy complications such as miscarriage, pre-eclampsia and intrauterine growth restriction. Despite the important role of placenta, the molecular mechanisms governing placental formation and trophoblast cell lineage specification is poorly understand. It is mostly due to the lack of appropriate model system. The great various in placental types across mammals make it limit for the use of laboratory animals in studying human placental development. However, over the past few years, alternative methods have been employed, including human embryonic stem cells, induced pluripotent stem cells, human trophoblast stem cell, and 3-dimensional organoids. Herein, we summarize the present knowledge about human development, differentiated cell types in the trophoblast epithelium and current human placental trophoblast model systems.

scholarly journals Pancreatic Progenitors and Organoids as a Prerequisite to Model Pancreatic Diseases and Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Meike Hohwieler ◽  
Martin Müller ◽  
Pierre-Olivier Frappart ◽  
Sandra Heller
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Embryonic Stem ◽  
Cell Types ◽  
Genetically Engineered ◽  
Hereditary Diseases ◽  
Pancreatic Diseases ◽  
Pancreatic Progenitors

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are characterized by their unique capacity to stepwise differentiate towards any particular cell type in an adult organism. Pluripotent stem cells provide a beneficial platform to model hereditary diseases and even cancer development. While the incidence of pancreatic diseases such as diabetes and pancreatitis is increasing, the understanding of the underlying pathogenesis of particular diseases remains limited. Only a few recent publications have contributed to the characterization of human pancreatic development in the fetal stage. Hence, most knowledge of pancreatic specification is based on murine embryology. Optimizing and understanding current in vitro protocols for pancreatic differentiation of ESCs and iPSCs constitutes a prerequisite to generate functional pancreatic cells for better disease modeling and drug discovery. Moreover, human pancreatic organoids derived from pluripotent stem cells, organ-restricted stem cells, and tumor samples provide a powerful technology to model carcinogenesis and hereditary diseases independent of genetically engineered mouse models. Herein, we summarize recent advances in directed differentiation of pancreatic organoids comprising endocrine cell types. Beyond that, we illustrate up-and-coming applications for organoid-based platforms.

scholarly journals Recent Overview of the Use of iPSCs Huntington’s Disease Modeling and Therapy

2020 ◽  
Vol 21 (6) ◽  
pp. 2239 ◽  
Author(s):  
Maria Csobonyeiova ◽  
Stefan Polak ◽  
Lubos Danisovic
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Disease Modeling ◽  
Cell Types ◽  
Cag Repeats ◽  
Neural Cells ◽  
Behavioral Impairment ◽  
Cell Based Therapy

Huntington’s disease (HD) is an inherited, autosomal dominant, degenerative disease characterized by involuntary movements, cognitive decline, and behavioral impairment ending in death. HD is caused by an expansion in the number of CAG repeats in the huntingtin gene on chromosome 4. To date, no effective therapy for preventing the onset or progression of the disease has been found, and many symptoms do not respond to pharmacologic treatment. However, recent results of pre-clinical trials suggest a beneficial effect of stem-cell-based therapy. Induced pluripotent stem cells (iPSCs) represent an unlimited cell source and are the most suitable among the various types of autologous stem cells due to their patient specificity and ability to differentiate into a variety of cell types both in vitro and in vivo. Furthermore, the cultivation of iPSC-derived neural cells offers the possibility of studying the etiopathology of neurodegenerative diseases, such as HD. Moreover, differentiated neural cells can organize into three-dimensional (3D) organoids, mimicking the complex architecture of the brain. In this article, we present a comprehensive review of recent HD models, the methods for differentiating HD–iPSCs into the desired neural cell types, and the progress in gene editing techniques leading toward stem-cell-based therapy.

scholarly journals Neural stem cells induce the formation of their physical niche during organogenesis

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Ali Seleit ◽  
Isabel Krämer ◽  
Bea F Riebesehl ◽  
Elizabeth M Ambrosio ◽  
Julian S Stolper ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Lineage ◽  
Cell Types ◽  
Neural Lineage ◽  
Posterior Lateral Line ◽  
4D Imaging ◽  
Outer Border ◽  
Embryonic Life ◽  
Independent Life ◽  
Necessary And Sufficient

Most organs rely on stem cells to maintain homeostasis during post-embryonic life. Typically, stem cells of independent lineages work coordinately within mature organs to ensure proper ratios of cell types. Little is known, however, on how these different stem cells locate to forming organs during development. Here we show that neuromasts of the posterior lateral line in medaka are composed of two independent life-long lineages with different embryonic origins. Clonal analysis and 4D imaging revealed a hierarchical organisation with instructing and responding roles: an inner, neural lineage induces the formation of an outer, border cell lineage (nBC) from the skin epithelium. Our results demonstrate that the neural lineage is necessary and sufficient to generate nBCs highlighting self-organisation principles at the level of the entire embryo. We hypothesise that induction of surrounding tissues plays a major role during the establishment of vertebrate stem cell niches.

scholarly journals Human Organoids for Predictive Toxicology Research and Drug Development

2021 ◽  
Vol 12 ◽  
Author(s):  
Toshikatsu Matsui ◽  
Tadahiro Shinozawa
Keyword(s):  
Stem Cells ◽  
Drug Development ◽  
Disease Modeling ◽  
Cell Types ◽  
Underlying Disease ◽  
Future Research ◽  
Specific Cell ◽  
Predictive Toxicology

Organoids are three-dimensional structures fabricated in vitro from pluripotent stem cells or adult tissue stem cells via a process of self-organization that results in the formation of organ-specific cell types. Human organoids are expected to mimic complex microenvironments and many of the in vivo physiological functions of relevant tissues, thus filling the translational gap between animals and humans and increasing our understanding of the mechanisms underlying disease and developmental processes. In the last decade, organoid research has attracted increasing attention in areas such as disease modeling, drug development, regenerative medicine, toxicology research, and personalized medicine. In particular, in the field of toxicology, where there are various traditional models, human organoids are expected to blaze a new path in future research by overcoming the current limitations, such as those related to differences in drug responses among species. Here, we discuss the potential usefulness, limitations, and future prospects of human liver, heart, kidney, gut, and brain organoids from the viewpoints of predictive toxicology research and drug development, providing cutting edge information on their fabrication methods and functional characteristics.

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