scholarly journals Tissues and Cell Types of Appendage Regeneration: A Detailed Look at the Wound Epidermis and Its Specialized Forms

2021 ◽  
Vol 12 ◽  
Author(s):  
Can Aztekin

Therapeutic implementation of human limb regeneration is a daring aim. Studying species that can regrow their lost appendages provides clues on how such a feat can be achieved in mammals. One of the unique features of regeneration-competent species lies in their ability to seal the amputation plane with a scar-free wound epithelium. Subsequently, this wound epithelium advances and becomes a specialized wound epidermis (WE) which is hypothesized to be the essential component of regenerative success. Recently, the WE and specialized WE terminologies have been used interchangeably. However, these tissues were historically separated, and contemporary limb regeneration studies have provided critical new information which allows us to distinguish them. Here, I will summarize tissue-level observations and recently identified cell types of WE and their specialized forms in different regeneration models.

Open Biology ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 210126
Author(s):  
Can Aztekin

Species that can regrow their lost appendages have been studied with the ultimate aim of developing methods to enable human limb regeneration. These examinations highlight that appendage regeneration progresses through shared tissue stages and gene activities, leading to the assumption that appendage regeneration paradigms (e.g. tails and limbs) are the same or similar. However, recent research suggests these paradigms operate differently at the cellular level, despite sharing tissue descriptions and gene expressions. Here, collecting the findings from disparate studies, I argue appendage regeneration is context dependent at the cellular level; nonetheless, it requires (i) signalling centres, (ii) stem/progenitor cell types and (iii) a regeneration-permissive environment, and these three common cellular principles could be more suitable for cross-species/paradigm/age comparisons.


1987 ◽  
Vol 65 (8) ◽  
pp. 739-749 ◽  
Author(s):  
Roy A. Tassava ◽  
David J. Goldhamer ◽  
Bruce L. Tomlinson

Data from pulse and continuous labeling with [3H]thymidine and from studies with monoclonal antibody WE3 have led to the modification of existing models and established concepts pertinent to understanding limb regeneration. Not all cells of the adult newt blastema are randomly distributed and actively progressing through the cell cycle. Instead, many cells are in a position that we have designated transient quiescence (TQ) and are not actively cycling. We postulate that cells regularly leave the TQ population and enter the actively cycling population and vice versa. The size of the TQ population may be at least partly determined by the quantity of limb innervation. Larval Ambystoma may have only a small or nonexisting TQ, thus accounting for their rapid rate of regeneration. Examination of reactivity of monoclonal antibody WE3 suggests that the early wound epithelium, which is derived from skin epidermis, is later replaced by cells from skin glands concomitant with blastema formation. WE3 provides a useful tool to further investigate the regenerate epithelium.


2018 ◽  
Vol 116 (1) ◽  
pp. 303-312 ◽  
Author(s):  
Erol C. Bayraktar ◽  
Lou Baudrier ◽  
Ceren Özerdem ◽  
Caroline A. Lewis ◽  
Sze Ham Chan ◽  
...  

Mitochondria are metabolic organelles that are essential for mammalian life, but the dynamics of mitochondrial metabolism within mammalian tissues in vivo remains incompletely understood. While whole-tissue metabolite profiling has been useful for studying metabolism in vivo, such an approach lacks resolution at the cellular and subcellular level. In vivo methods for interrogating organellar metabolites in specific cell types within mammalian tissues have been limited. To address this, we built on prior work in which we exploited a mitochondrially localized 3XHA epitope tag (MITO-Tag) for the fast isolation of mitochondria from cultured cells to generate MITO-Tag Mice. Affording spatiotemporal control over MITO-Tag expression, these transgenic animals enable the rapid, cell-type-specific immunoisolation of mitochondria from tissues, which we verified using a combination of proteomic and metabolomic approaches. Using MITO-Tag Mice and targeted and untargeted metabolite profiling, we identified changes during fasted and refed conditions in a diverse array of mitochondrial metabolites in hepatocytes and found metabolites that behaved differently at the mitochondrial versus whole-tissue level. MITO-Tag Mice should have utility for studying mitochondrial physiology, and our strategy should be generally applicable for studying other mammalian organelles in specific cell types in vivo.


2018 ◽  
Author(s):  
Erol Can Bayraktar ◽  
Lou Baudrier ◽  
Ceren Özerdem ◽  
Caroline A. Lewis ◽  
Sze Ham Chan ◽  
...  

ABSTRACTMitochondria are metabolic organelles that are essential for mammalian life, but the dynamics of mitochondrial metabolism within mammalian tissues in vivo remains incompletely understood. While whole-tissue metabolite profiling has been useful for studying metabolism in vivo, such an approach lacks resolution at the cellular and subcellular level. In vivo methods for interrogating organellar metabolites in specific cell-types within mammalian tissues have been limited. To address this, we built on prior work in which we exploited a mitochondrially-localized 3XHA epitope-tag (“MITO-Tag”) for the fast isolation of mitochondria from cultured cells to now generate “MITO-Tag Mice.” Affording spatiotemporal control over MITO-Tag expression, these transgenic animals enable the rapid, cell-type-specific immunoisolation of mitochondria from tissues, which we verified using a combination of proteomic and metabolomic approaches. Using MITO-Tag Mice and targeted and untargeted metabolite profiling, we identified changes during fasted and refed conditions in a diverse array of mitochondrial metabolites in hepatocytes and found metabolites that behaved differently at the mitochondrial versus whole-tissue level. MITO-Tag Mice should have utility for studying mitochondrial physiology and our strategy should be generally applicable for studying other mammalian organelles in specific cell-types in vivo.


2019 ◽  
Author(s):  
Gemma L. Johnson ◽  
Erick J. Masias ◽  
Jessica A. Lehoczky

ABSTRACTInnate regeneration following digit tip amputation is one of the few examples of epimorphic regeneration in mammals. Digit tip regeneration is mediated by the blastema, the same structure invoked during limb regeneration in some lower vertebrates. By genetic lineage analyses in mice, the digit tip blastema has been defined as a population of heterogeneous, lineage restricted progenitor cells. These previous studies, however, do not comprehensively evaluate blastema heterogeneity or address lineage restriction of closely related cell types. In this report we present single cell RNA sequencing of over 38,000 cells from mouse digit tip blastemas and unamputated control digit tips and generate an atlas of the cell types participating in digit tip regeneration. We define the differentiation trajectories of vascular, monocytic, and fibroblastic lineages over regeneration, and while our data confirm broad lineage restriction of progenitors, our analysis reveals an early blastema fibroblast population expressing a novel regeneration-specific gene, Mest.


2013 ◽  
Vol 35 (1) ◽  
pp. 39 ◽  
Author(s):  
Hayley J. Stannard ◽  
Julie M. Old

This paper provides a macro- and microscopic description of the digestive tract of the kultarr (Antechinomys laniger), a small dasyurid marsupial. The digestive tract was simple, with no external differentiation between the small and large intestine, and lacked a caecum. Mean gross length of the kultarr digestive tract was 165.2 ± 32.1 mm. Microscopically, the tissues had cell types similar to those of other mammals. The new information will aid future post-mortem investigations of captive kultarrs and future studies of nutrition.


2020 ◽  
Vol 8 (1) ◽  
pp. e000363 ◽  
Author(s):  
Samuel Chuah ◽  
Valerie Chew

Immunotherapy is a rapidly growing field for cancer treatment. In contrast to conventional cancer therapies, immunotherapeutic strategies focus on reactivating the immune system to mount an antitumor response. Despite the encouraging outcome in clinical trials, a large proportion of patients still do not respond to treatment and many experience different degrees of immune-related adverse events. Furthermore, it is now increasingly appreciated that even many conventional cancer therapies such as radiotherapy could have a positive impact on the host immune system for better clinical response. Hence, there is a need to better understand tumor immunity in order to design immunotherapeutic strategies, especially evidence-based combination therapies, for improved clinical outcomes. With this aim, cancer research turned its attention to profiling the immune contexture of either the tumor microenvironment (TME) or peripheral blood to uncover mechanisms and biomarkers which might aid in precision immunotherapeutics. Conventional technologies used for this purpose were limited by the depth and dimensionality of the data. Advances in newer techniques have, however, greatly improved the breadth and depth, as well as the quantity and quality of data that can be obtained. The result of these advances is a wealth of new information and insights on how the TME could be affected by various immune cell-types, and how this might in turn impact the clinical outcome of cancer patients . We highlight herein some of the high-dimensional technologies currently employed in immune profiling in cancer and summarize the insights and potential benefits they could bring in designing better cancer immunotherapies.


2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Ana J. Chucair-Elliott ◽  
Sarah R. Ocañas ◽  
David R. Stanford ◽  
Victor A. Ansere ◽  
Kyla B. Buettner ◽  
...  

AbstractEpigenetic regulation of gene expression occurs in a cell type-specific manner. Current cell-type specific neuroepigenetic studies rely on cell sorting methods that can alter cell phenotype and introduce potential confounds. Here we demonstrate and validate a Nuclear Tagging and Translating Ribosome Affinity Purification (NuTRAP) approach for temporally controlled labeling and isolation of ribosomes and nuclei, and thus RNA and DNA, from specific central nervous system cell types. Analysis of gene expression and DNA modifications in astrocytes or microglia from the same animal demonstrates differential usage of DNA methylation and hydroxymethylation in CpG and non-CpG contexts that corresponds to cell type-specific gene expression. Application of this approach in LPS treated mice uncovers microglia-specific transcriptome and epigenome changes in inflammatory pathways that cannot be detected with tissue-level analysis. The NuTRAP model and the validation approaches presented can be applied to any brain cell type for which a cell type-specific cre is available.


1981 ◽  
Vol 241 (3) ◽  
pp. F203-F218 ◽  
Author(s):  
H. R. Jacobson

Although each of the major experimental techniques applied to the study of renal physiology has provided its fair share of new information, the technique of in vitro microperfusion of nephron segments is notable for two major contributions. First, it has supplied a more direct and controlled means of studying epithelial transport processes, some of which already have helped us to understand certain aspects of kidney function and others of which have yet to find their application in unraveling the mysteries of the kidney. Second, in the process of delineating these transport characteristics, it has served to emphasize the epithelial specialization present in the kidney, providing functional counterparts to the already recognized anatomic heterogeneity present in the kidney. In this second role microperfusion has spawned the application of biochemical analysis of the hormonal responses of various nephron segments and contributed to the impetus for work in culturing the various cell types present in each nephron segment. This review outlines the functional characteristics of the 11 major segments of the nephron, incorporating what has been learned from some of the biochemical work on hormone response and correlating the latter with transport events.


2000 ◽  
Vol 88 (5) ◽  
pp. 1880-1889 ◽  
Author(s):  
Navdeep S. Chandel ◽  
Paul T. Schumacker

Hypoxia elicits a variety of adaptive responses at the tissue level, at the cellular level, and at the molecular level. A physiological response to hypoxia requires the existence of an O2sensor coupled to a signal transduction system, which in turn activates the functional response. Although much has been learned about the signaling systems activated by hypoxia, no consensus exists regarding the nature of the underlying O2sensor or whether multiple sensors exist. Among previously considered mechanisms, heme proteins have been suggested to undergo allosteric modification in response to O2binding or release at different [Formula: see text] levels. Other studies suggest that ion channels may change conductance as a function of[Formula: see text], allowing them to signal the onset of hypoxia. Still other studies suggest that NADPH oxidase may decrease its generation of reactive O2species (ROS) during hypoxia. Recent data suggest that mitochondria may function as O2sensors by increasing their generation of ROS during hypoxia. These oxidant signals appear to act as second messengers in the adaptive responses to hypoxia in a variety of cell types. Such observations contribute to a growing awareness that mitochondria do more than just generate ATP, in that they initiate signaling cascades involved in adaptive responses to hypoxia and that they participate in the control of cell death pathways.


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