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Frontiers in Immunology 2023During development, cortical (c) and medullary (m) thymic epithelial cells (TEC) arise from the third pharyngeal pouch endoderm. Current models suggest that within the...
During development, cortical (c) and medullary (m) thymic epithelial cells (TEC) arise from the third pharyngeal pouch endoderm. Current models suggest that within the thymic primordium most TEC exist in a bipotent/common thymic epithelial progenitor cell (TEPC) state able to generate both cTEC and mTEC, at least until embryonic day 12.5 (E12.5) in the mouse. This view, however, is challenged by recent transcriptomics and genetic evidence. We therefore set out to investigate the fate and potency of TEC in the early thymus. Here using single cell (sc) RNAseq we identify a candidate mTEC progenitor population at E12.5, consistent with recent reports. Via lineage-tracing we demonstrate this population as mTEC fate-restricted, validating our bioinformatics prediction. Using potency analyses we also establish that most E11.5 and E12.5 progenitor TEC are cTEC-fated. Finally we show that overnight culture causes most if not all E12.5 cTEC-fated TEPC to acquire functional bipotency, and provide a likely molecular mechanism for this changed differentiation potential. Collectively, our data overturn the widely held view that a common TEPC predominates in the E12.5 thymus, showing instead that sublineage-primed progenitors are present from the earliest stages of thymus organogenesis but that these early fetal TEPC exhibit cell-fate plasticity in response to extrinsic factors. Our data provide a significant advance in the understanding of fetal thymic epithelial development and thus have implications for thymus-related clinical research, in particular research focussed on generating TEC from pluripotent stem cells.
Topics: Mice; Animals; Epithelial Cells; Cell Differentiation; Thymus Gland; Organogenesis; Embryonic Stem Cells
PubMed: 37559721
DOI: 10.3389/fimmu.2023.1202163 -
Nature Reviews. Nephrology Feb 20202019 saw advances in the generation of induced pluripotent stem cell (iPSC)-derived nephron progenitors and in our understanding of how nephrons form in a kidney... (Review)
Review
2019 saw advances in the generation of induced pluripotent stem cell (iPSC)-derived nephron progenitors and in our understanding of how nephrons form in a kidney organoid. Fundamental studies of regeneration in zebra fish continue to provide vital clues as to how we might use iPSC-derived cells to regenerate a human nephron in vivo.
Topics: Animals; Cell Differentiation; Humans; Induced Pluripotent Stem Cells; Nephrons; Organogenesis; Organoids; Regeneration; Stem Cells; Zebrafish
PubMed: 31811252
DOI: 10.1038/s41581-019-0238-0 -
Nature Reviews. Endocrinology Mar 2018A remarkable, unexpected aspect of the bone-derived hormone osteocalcin is that it is necessary for both brain development and brain function in the mouse, as its... (Review)
Review
A remarkable, unexpected aspect of the bone-derived hormone osteocalcin is that it is necessary for both brain development and brain function in the mouse, as its absence results in a profound deficit in spatial learning and memory and an exacerbation of anxiety-like behaviour. The regulation of cognitive function by osteocalcin, together with the fact that its circulating levels decrease in midlife compared with adolescence in all species tested, raised the prospect that osteocalcin might be an anti-geronic hormone that could prevent age-related cognitive decline. As presented in this Review, recent data indicate that this is indeed the case and that osteocalcin is necessary for the anti-geronic activity recently ascribed to the plasma of young wild-type mice. The diversity and amplitude of the functions of osteocalcin in the brain, during development and postnatally, had long called for the identification of its receptor in the brain, which was also recently achieved. This Review presents our current understanding of the biology of osteocalcin in the brain, highlighting the bony vertebrate specificity of the regulation of cognitive function and pointing toward where therapeutic opportunities might exist.
Topics: Adolescent; Adult; Age Factors; Aging; Animals; Bone and Bones; Brain; Cognition; Cognitive Dysfunction; Humans; Mice; Organogenesis; Osteocalcin; Sensitivity and Specificity; Spatial Learning
PubMed: 29376523
DOI: 10.1038/nrendo.2017.181 -
PloS One 2018The notochord is a major regulator of embryonic patterning in vertebrates and abnormal notochordal development is associated with a variety of birth defects in man....
The notochord is a major regulator of embryonic patterning in vertebrates and abnormal notochordal development is associated with a variety of birth defects in man. Proper knowledge of the development of the human notochord, therefore, is important to understand the pathogenesis of these birth defects. Textbook descriptions vary significantly and seem to be derived from both human and animal data whereas the lack of references hampers verification of the presented data. Therefore, a verifiable and comprehensive description of the development of the human notochord is needed. Our analysis and three-dimensional (3D) reconstructions of 27 sectioned human embryos ranging from Carnegie Stage 8 to 15 (17-41 days of development), resulted in a comprehensive and verifiable new model of notochordal development. Subsequent to gastrulation, a transient group of cells briefly persists as the notochordal process which is incorporated into the endodermal roof of the gut while its dorsal side attaches to the developing neural tube. Then, the notochordal process embeds entirely into the endoderm, forming the epithelial notochordal plate, which remains intimately associated with the neural tube. Subsequently, the notochordal cells detach from the endoderm to form the definitive notochord, allowing the paired dorsal aortae to fuse between the notochord and the gut. We show that the formation of the notochordal process and plate proceeds in cranio-caudal direction. Moreover, in contrast to descriptions in the modern textbooks, we report that the formation of the definitive notochord in humans starts in the middle of the embryo, and proceeds in both cranial and caudal directions.
Topics: Embryo, Mammalian; Humans; Imaging, Three-Dimensional; Models, Anatomic; Models, Biological; Notochord; Organogenesis
PubMed: 30346967
DOI: 10.1371/journal.pone.0205752 -
Cells Jun 2022TNF and LTα are structurally related cytokines of the TNF superfamily. Their genes are located in close proximity to each other and to the gene within the TNF/LT locus...
TNF and LTα are structurally related cytokines of the TNF superfamily. Their genes are located in close proximity to each other and to the gene within the TNF/LT locus inside MHC. Unlike , transcription of and of is tightly controlled, with the gene being an immediate early gene that is rapidly induced in response to various inflammatory stimuli. Genes of the TNF/LT locus play a crucial role in lymphoid tissue organogenesis, although some aspects of their specific contribution remain controversial. Here, we present new findings and discuss the distinct contribution of TNF produced by ILC3 cells to Peyer's patch organogenesis.
Topics: Animals; Lymphoid Tissue; Lymphotoxin-alpha; Mice; Mice, Knockout; Organogenesis; Peyer's Patches; Tumor Necrosis Factors
PubMed: 35741098
DOI: 10.3390/cells11121970 -
Pediatric Nephrology (Berlin, Germany) Apr 2014The nephron is the functional unit that executes the homeostatic roles of the kidney in vertebrates. Critical to this function is the physical arrangement of the... (Review)
Review
The nephron is the functional unit that executes the homeostatic roles of the kidney in vertebrates. Critical to this function is the physical arrangement of the glomerular blood filter attached to a tubular epithelium that is subdivided into specialized proximal and distal segments. During embryogenesis, nephron progenitors undergo a mesenchymal-epithelial transition (MET) and adopt different segment-specific cell fates along the proximo-distal axis of the nephron. The molecular basis of how these segments arise remains largely unknown. Recent studies using the zebrafish have identified the Hnf1beta transcription factor (Hnf1b) as a major regulator of tubular segmentation. In Hnf1b-deficient zebrafish embryos, nephron progenitors fail to adopt the proximo-distal segmentation pattern of the nephron, yet still undergo MET. This observation suggests that the functional segmentation of renal tubular epithelial cells is independent of pathways that induce their epithelialization. Here we review this new role of Hnf1b for nephron segmentation during zebrafish and mouse kidney development.
Topics: Animals; Hepatocyte Nuclear Factor 1-beta; Humans; Nephrons; Organogenesis; Zebrafish Proteins
PubMed: 24190171
DOI: 10.1007/s00467-013-2662-x -
Differentiation; Research in Biological... 2016Significant recent advances in methodologies for the differentiation of pluripotent stem cells to renal progenitors as well as the definition of niche conditions for... (Review)
Review
Significant recent advances in methodologies for the differentiation of pluripotent stem cells to renal progenitors as well as the definition of niche conditions for sustaining those progenitors have dramatically enhanced our understanding of their biology and developmental programing, prerequisites for establishing viable approaches to renal regeneration. In this article, we review the evolution of culture techniques and models for the study of metanephric development, describe the signaling mechanisms likely to be driving progenitor self-renewal, and discuss current efforts to generate de novo functional tissues, providing in depth protocols and niche conditions for the stabilization of the nephronic Six2+progenitor.
Topics: Cell Differentiation; Humans; Kidney; Nephrons; Organogenesis; Pluripotent Stem Cells; Regeneration; Signal Transduction
PubMed: 26856661
DOI: 10.1016/j.diff.2016.01.007 -
Trends in Genetics : TIG Jun 2015Defining how organ size is regulated, a process controlled not only by the number of cells but also by the size of the cells, is a frontier in developmental biology.... (Review)
Review
Defining how organ size is regulated, a process controlled not only by the number of cells but also by the size of the cells, is a frontier in developmental biology. Large cells are produced by increasing DNA content or ploidy, a developmental strategy employed throughout the plant and animal kingdoms. The widespread use of polyploidy during cell differentiation makes it important to define how this hypertrophy contributes to organogenesis. I discuss here examples from a variety of animals and plants in which polyploidy controls organ size, the size and function of specific tissues within an organ, or the differentiated properties of cells. In addition, I highlight how polyploidy functions in wound healing and tissue regeneration.
Topics: Animals; Cell Cycle; Cell Differentiation; Cell Size; Models, Genetic; Organ Size; Organogenesis; Plant Cells; Polyploidy; Wound Healing
PubMed: 25921783
DOI: 10.1016/j.tig.2015.03.011 -
Seminars in Cell & Developmental Biology Aug 2018Vertebrate embryonic development requires specific signaling events that regulate cell proliferation and differentiation to occur at the correct place and the correct... (Review)
Review
Vertebrate embryonic development requires specific signaling events that regulate cell proliferation and differentiation to occur at the correct place and the correct time in order to build a healthy embryo. Signaling pathways are sensitive to perturbations of the endogenous redox state, and are also susceptible to modulation by reactive species and antioxidant defenses, contributing to a spectrum of passive vs. active effects that can affect redox signaling and redox stress. Here we take a multi-level, integrative approach to discuss the importance of redox status for vertebrate developmental signaling pathways and cell fate decisions, with a focus on glutathione/glutathione disulfide, thioredoxin, and cysteine/cystine redox potentials and the implications for protein function in development. We present a tissue-specific example of the important role that reactive species play in pancreatic development and metabolic regulation. We discuss NFE2L2 (also known as NRF2) and related proteins, their roles in redox signaling, and their regulation of glutathione during development. Finally, we provide examples of xenobiotic compounds that disrupt redox signaling in the context of vertebrate embryonic development. Collectively, this review provides a systems-level perspective on the innate and inducible antioxidant defenses, as well as their roles in maintaining redox balance during chemical exposures that occur in critical windows of development.
Topics: Animals; Cell Differentiation; Cell Proliferation; Embryonic Development; Humans; Organogenesis; Oxidation-Reduction; Reactive Oxygen Species
PubMed: 28927759
DOI: 10.1016/j.semcdb.2017.09.019 -
Anatomical Record (Hoboken, N.J. : 2007) Oct 2020Branching morphogenesis is an integral developmental mechanism central to the formation of a range of organs including the kidney, lung, pancreas and mammary gland. The... (Review)
Review
Branching morphogenesis is an integral developmental mechanism central to the formation of a range of organs including the kidney, lung, pancreas and mammary gland. The ramified networks of epithelial tubules it establishes are critical for the processes of secretion, excretion and exchange mediated by these tissues. In the kidney, branching serves to establish the collecting duct system that transports urine from the nephrons into the renal pelvis, ureter and finally the bladder. Generally speaking, the formation of these networks in different organs begins with the specification and differentiation of simple bud-like organ anlage, which then undergo a process of elaboration, typically by bifurcation. This process is often governed by the interaction of progenitor cells at the tips of the epithelia with neighboring mesenchymal cell populations which direct the branching process and which often themselves differentiate to form part of the adult organ. In the kidney, the tips of ureteric bud elaborate through a dynamic cell signaling relationship with overlying nephron progenitor cell populations. These cells sequentially commit to differentiation and the resulting nephrons reintegrate with the ureteric epithelium as development progresses. This review will describe recent advances in understanding the how the elaboration of the ureteric bud is patterned and consider the extent to which this process is shared with other organs.
Topics: Cell Differentiation; Humans; Kidney; Organogenesis; Stem Cells
PubMed: 32790143
DOI: 10.1002/ar.24486