scholarly journals Adult tissue-resident stem cells—fact or fiction?

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Deepa Bhartiya
Keyword(s):  
Stem Cells ◽  
Single Cell ◽  
Adult Stem Cells ◽  
Cell Types ◽  
Specific Cell ◽  
Tissue Specific ◽  
Cardiac Tissues ◽  
Adult Tissues ◽  
Resident Stem Cells ◽  
Abundant Cytoplasm

AbstractLife-long tissue homeostasis of adult tissues is supposedly maintained by the resident stem cells. These stem cells are quiescent in nature and rarely divide to self-renew and give rise to tissue-specific “progenitors” (lineage-restricted and tissue-committed) which divide rapidly and differentiate into tissue-specific cell types. However, it has proved difficult to isolate these quiescent stem cells as a physical entity. Recent single-cell RNAseq studies on several adult tissues including ovary, prostate, and cardiac tissues have not been able to detect stem cells. Thus, it has been postulated that adult cells dedifferentiate to stem-like state to ensure regeneration and can be defined as cells capable to replace lost cells through mitosis. This idea challenges basic paradigm of development biology regarding plasticity that a cell enters point of no return once it initiates differentiation. The underlying reason for this dilemma is that we are putting stem cells and somatic cells together while processing for various studies. Stem cells and adult mature cell types are distinct entities; stem cells are quiescent, small in size, and with minimal organelles whereas the mature cells are metabolically active and have multiple organelles lying in abundant cytoplasm. As a result, they do not pellet down together when centrifuged at 100–350g. At this speed, mature cells get collected but stem cells remain buoyant and can be pelleted by centrifuging at 1000g. Thus, inability to detect stem cells in recently published single-cell RNAseq studies is because the stem cells were unknowingly discarded while processing and were never subjected to RNAseq. This needs to be kept in mind before proposing to redefine adult stem cells.

scholarly journals Polycomb Repressive Complex(es) and Their Role in Adult Stem Cells

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1485
Author(s):  
Pooja Flora ◽  
Gil Dalal ◽  
Idan Cohen ◽  
Elena Ezhkova
Keyword(s):  
Stem Cells ◽  
Adult Stem Cells ◽  
Adult Stem Cell ◽  
Cell Types ◽  
Polycomb Group ◽  
Polycomb Repressive Complex ◽  
Cell Compartments ◽  
Adult Tissues ◽  
Resident Stem Cells ◽  
And Function

Populations of resident stem cells (SCs) are responsible for maintaining, repairing, and regenerating adult tissues. In addition to having the capacity to generate all the differentiated cell types of the tissue, adult SCs undergo long periods of quiescence within the niche to maintain themselves. The process of SC renewal and differentiation is tightly regulated for proper tissue regeneration throughout an organisms’ lifetime. Epigenetic regulators, such as the polycomb group (PcG) of proteins have been implicated in modulating gene expression in adult SCs to maintain homeostatic and regenerative balances in adult tissues. In this review, we summarize the recent findings that elucidate the composition and function of the polycomb repressive complex machinery and highlight their role in diverse adult stem cell compartments.

scholarly journals Mesenchymal Stem Cells Isolated from Adipose and Other Tissues: Basic Biological Properties and Clinical Applications

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Hakan Orbay ◽  
Morikuni Tobita ◽  
Hiroshi Mizuno
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adult Stem Cells ◽  
Cell Types ◽  
Biological Properties ◽  
Clinical Applications ◽  
Therapeutic Tool ◽  
Adult Tissues ◽  
Clinical Benefits ◽  
Multiple Cell

Mesenchymal stem cells (MSCs) are adult stem cells that were initially isolated from bone marrow. However, subsequent research has shown that other adult tissues also contain MSCs. MSCs originate from mesenchyme, which is embryonic tissue derived from the mesoderm. These cells actively proliferate, giving rise to new cells in some tissues, but remain quiescent in others. MSCs are capable of differentiating into multiple cell types including adipocytes, chondrocytes, osteocytes, and cardiomyocytes. Isolation and induction of these cells could provide a new therapeutic tool for replacing damaged or lost adult tissues. However, the biological properties and use of stem cells in a clinical setting must be well established before significant clinical benefits are obtained. This paper summarizes data on the biological properties of MSCs and discusses current and potential clinical applications.

scholarly journals The E3 Ligase Axotrophin/MARCH-7: Protein Expression Profiling of Human Tissues Reveals Links to Adult Stem Cells

2009 ◽  
Vol 58 (4) ◽  
pp. 301-308 ◽  
Author(s):  
Cristina A. Szigyarto ◽  
Paul Sibbons ◽  
Gill Williams ◽  
Mathias Uhlen ◽  
Su M. Metcalfe
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Protein Expression ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
Null Mouse ◽  
Specific Cell ◽  
Direct Role ◽  
Neuronal Progenitor

Axotrophin/MARCH-7 was first identified in mouse embryonic stem cells as a neural stem cell gene. Using the axotrophin/MARCH-7 null mouse, we discovered profound effects on T lymphocyte responses, including 8-fold hyperproliferation and 5-fold excess release of the stem cell cytokine leukemia inhibitory factor (LIF). Our further discovery that axotrophin/MARCH-7 is required for targeted degradation of the LIF receptor subunit gp190 implies a direct role in the regulation of LIF signaling. Bioinformatics studies revealed a highly conserved RING-CH domain in common with the MARCH family of E3-ubiquitin ligases, and accordingly, axotrophin was renamed “MARCH-7.” To probe protein expression of human axotrophin/MARCH-7, we prepared antibodies against different domains of the protein. Each antibody bound its specific target epitope with high affinity, and immunohistochemistry cross-validated target specificity. Forty-eight human tissue types were screened. Epithelial cells stained strongly, with trophoblasts having the greatest staining. In certain tissues, specific cell types were selectively positive, including neurons and neuronal progenitor cells in the hippocampus and cerebellum, endothelial sinusoids of the spleen, megakaryocytes in the bone marrow, crypt stem cells of the small intestine, and alveolar macrophages in the lung. Approximately 20% of central nervous system neuropils were positive. Notably, axotrophin/MARCH-7 has an expression profile that is distinct from that of other MARCH family members. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials.

scholarly journals SCISSOR™: a single-cell inferred site-specific omics resource for tumor microenvironment association study

NAR Cancer ◽  
2021 ◽  
Vol 3 (3) ◽  
Author(s):  
Xiang Cui ◽  
Fei Qin ◽  
Xuanxuan Yu ◽  
Feifei Xiao ◽  
Guoshuai Cai
Keyword(s):  
Tumor Microenvironment ◽  
Single Cell ◽  
Clinical Outcomes ◽  
Large Scale ◽  
Cell Types ◽  
Cell Interaction ◽  
Specific Cell ◽  
Dynamic Visualization ◽  
Tissue Specific ◽  
Cell Composition

Abstract Tumor tissues are heterogeneous with different cell types in tumor microenvironment, which play an important role in tumorigenesis and tumor progression. Several computational algorithms and tools have been developed to infer the cell composition from bulk transcriptome profiles. However, they ignore the tissue specificity and thus a new resource for tissue-specific cell transcriptomic reference is needed for inferring cell composition in tumor microenvironment and exploring their association with clinical outcomes and tumor omics. In this study, we developed SCISSOR™ (https://thecailab.com/scissor/), an online open resource to fulfill that demand by integrating five orthogonal omics data of >6031 large-scale bulk samples, patient clinical outcomes and 451 917 high-granularity tissue-specific single-cell transcriptomic profiles of 16 cancer types. SCISSOR™ provides five major analysis modules that enable flexible modeling with adjustable parameters and dynamic visualization approaches. SCISSOR™ is valuable as a new resource for promoting tumor heterogeneity and tumor–tumor microenvironment cell interaction research, by delineating cells in the tissue-specific tumor microenvironment and characterizing their associations with tumor omics and clinical outcomes.

Human Mesenchymal Stem Cells Differentiate Promptly into Tissue-Specific Cell Types without Cell Fusion, Mitochondrial or Membrane Vesicular Transfer in Fetal Sheep.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 436-436 ◽  
Author(s):  
Evan J. Colletti ◽  
Judith A. Airey ◽  
Esmail D. Zanjani ◽  
Christopher D. Porada ◽  
Graça Almeida-Porada
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Fusion ◽  
Human Mesenchymal Stem Cells ◽  
Cell Types ◽  
Specific Cell ◽  
Type I ◽  
Fetal Sheep ◽  
Tissue Specific ◽  
The Brain

Abstract Despite the exciting reports regarding the ability of human mesenchymal stem cells (MSC) to differentiate into different cells of different organs, the mechanism by which this process occurs remains controversial. Several possible explanations have been put forth as an alternative to the existence of a true differentiation mechanism. We previously showed that MSC, at a single cell level, are able to differentiate into cells of different germ cell layers. In the present study, we investigated whether transfer of mitochondria or membrane-derived vesicles between cells and/or cell fusion participate in the events that lead to the change of phenotype of MSC upon transplantation (Tx). To this end, 54 sheep fetuses (55–60 gestational days) were Tx intra-peritoneally with Stro-1+,CD45−, Gly-A- MSC labeled prior to Tx with either CFSE, that irreversibly couples to both intracellular and cell-surface proteins, or DiD that efficiently labels all cell membranes and intracellular organelles, such as mitochondria. Evaluation of the recipients’ different organs started at 20h post-Tx and continued at 25,30,40,60 and 120h. MSC reached the liver at 25h post-Tx (0.033%±0.0) with maximal engraftment at 40h (0.13%±0.02). MSC were first detected in the lung (0.028%±0.0) and brain (0.034%±0.0) at 30h and 40h respectively. In the brain, engraftment peaked at 60 hours post-Tx (0.08%±0.0) and in the lung at 120h (0.09%±0.01). Normalization of the number of engrafted cells per tissue mass and number of Tx cells revealed that 26% of the Tx MSC reached the lung; 2% the liver; and 3% the brain. Since the decreasing number of CFSE+ and DiD+ cells detected after 120h could be due to cell division, Ki67 staining was performed and revealed that 85–95% of the engrafted cells proliferated upon lodging in the organs, and divided throughout the evaluation period. To determine MSC differentiative timeline, confocal microscopy was performed to assess whether CFSE+ or DiD+ cells expressed tissue-specific markers (MSC were negative for these markers prior to transplant) within the engrafted organs. In the liver at 25h post-Tx, all CFSE+ or DiD+ cells co-expressed alpha-fetoprotein, demonstrating the rapid switch from an MSC to a fetal hepatocyte-like phenotype. In the lung, co-localization of pro-surfactant protein and CFSE/DiD was first detected at 30h post-Tx, but cells remained negative for Caveolin1; a phenotype that is consistent with differentiation to a type II epithelial cell, but not to a more mature type I. In the brain, MSC expressed Tau promptly, but synaptophysin expression was not detected until 120h. In situ hybridization on serial sections using either a human- or sheep-specific probe, with simultaneous visualization of CFSE+ or DiD+ cells allowed us to show that no membrane or mitochondrial transfer had occurred, since none of the sheep cells contained CFSE or DiD, and all of the dye+ cells hybridized only to the human probe. Furthermore, this combined methodology enabled us to determine that differentiation to all of the different cell types had occurred in the absence of cell fusion. In conclusion, MSC engraft multiple tissues rapidly, undergo proliferation, and give rise to tissue-specific cell types in the absence of cellular fusion or the transfer of mitochondria or membrane vesicles.

scholarly journals Liver Cancer Stem Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Sameh Mikhail ◽  
Aiwu Ruth He
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Adult Stem Cells ◽  
Cell Types ◽  
Specific Cell ◽  
Solid Cancer ◽  
Primary Malignancy ◽  
Liver Cancer Stem Cells

Hepatocellular carcinoma is the most common primary malignancy of the liver in adults. It is also the fifth most common solid cancer worldwide and the third leading cause of cancer-related death. Recent research supports that liver cancer is a disease of adult stem cells. From the models of experimental hepatocarcinogenesis, there may be at least three distinct cell lineages with progenitor properties susceptible to neoplastic transformation. Identification of specific cell surface markers for each of the liver cell types, production of corresponding monoclonal antibodies and cell sorting techniques have together revolutionized the characteristics of normal stem cells. In hepatocarcinogenesis, multiple signaling transduction pathways, important for stem cell proliferation and differentiations, are deregulated. Strategies are being developed to identify and characterize the liver cancer stem cells. Targeting liver cancer stem cells may bring hope to curing hepatocellular carcinoma.

scholarly journals A practical solution to pseudoreplication bias in single-cell studies

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kip D. Zimmerman ◽  
Mark A. Espeland ◽  
Carl D. Langefeld
Keyword(s):  
Single Cell ◽  
Mixed Models ◽  
Random Effect ◽  
Cell Types ◽  
Error Rates ◽  
Specific Cell ◽  
Experimental Conditions ◽  
Type 1 Error ◽  
Sample Correlation ◽  
Inflated Type

AbstractCells from the same individual share common genetic and environmental backgrounds and are not statistically independent; therefore, they are subsamples or pseudoreplicates. Thus, single-cell data have a hierarchical structure that many current single-cell methods do not address, leading to biased inference, highly inflated type 1 error rates, and reduced robustness and reproducibility. This includes methods that use a batch effect correction for individual as a means of accounting for within-sample correlation. Here, we document this dependence across a range of cell types and show that pseudo-bulk aggregation methods are conservative and underpowered relative to mixed models. To compute differential expression within a specific cell type across treatment groups, we propose applying generalized linear mixed models with a random effect for individual, to properly account for both zero inflation and the correlation structure among measures from cells within an individual. Finally, we provide power estimates across a range of experimental conditions to assist researchers in designing appropriately powered studies.

scholarly journals Histone Acetyltransferases and Stem Cell Identity

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2407
Author(s):  
Ruicen He ◽  
Arthur Dantas ◽  
Karl Riabowol
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Epigenetic Modification ◽  
Cell Types ◽  
Histone Acetyltransferases ◽  
Specific Cell ◽  
Cell Fates ◽  
Cell Identity ◽  
Hematopoietic Stem

Acetylation of histones is a key epigenetic modification involved in transcriptional regulation. The addition of acetyl groups to histone tails generally reduces histone-DNA interactions in the nucleosome leading to increased accessibility for transcription factors and core transcriptional machinery to bind their target sequences. There are approximately 30 histone acetyltransferases and their corresponding complexes, each of which affect the expression of a subset of genes. Because cell identity is determined by gene expression profile, it is unsurprising that the HATs responsible for inducing expression of these genes play a crucial role in determining cell fate. Here, we explore the role of HATs in the maintenance and differentiation of various stem cell types. Several HAT complexes have been characterized to play an important role in activating genes that allow stem cells to self-renew. Knockdown or loss of their activity leads to reduced expression and or differentiation while particular HATs drive differentiation towards specific cell fates. In this study we review functions of the HAT complexes active in pluripotent stem cells, hematopoietic stem cells, muscle satellite cells, mesenchymal stem cells, neural stem cells, and cancer stem cells.

scholarly journals Single-cell analysis of human adipose tissue identifies depot- and disease-specific cell types

2019 ◽  
Vol 2 (1) ◽  
pp. 97-109 ◽  
Author(s):  
Jinchu Vijay ◽  
Marie-Frédérique Gauthier ◽  
Rebecca L. Biswell ◽  
Daniel A. Louiselle ◽  
Jeffrey J. Johnston ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Single Cell ◽  
Single Cell Analysis ◽  
Human Adipose Tissue ◽  
Cell Types ◽  
Specific Cell ◽  
Cell Analysis ◽  
Disease Specific

scholarly journals Collagen gel three-dimensional matrices combined with adhesive proteins stimulate neuronal differentiation of mesenchymal stem cells

2011 ◽  
Vol 8 (60) ◽  
pp. 998-1010 ◽  
Author(s):  
Jae Ho Lee ◽  
Hye-Sun Yu ◽  
Gil-Su Lee ◽  
Aeri Ji ◽  
Jung Keun Hyun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Neuronal Differentiation ◽  
Large Population ◽  
Three Dimensional ◽  
Collagen Gel ◽  
Cell Types ◽  
Specific Cell ◽  
Neuronal Outgrowth ◽  
Adhesive Proteins

Three-dimensional gel matrices provide specialized microenvironments that mimic native tissues and enable stem cells to grow and differentiate into specific cell types. Here, we show that collagen three-dimensional gel matrices prepared in combination with adhesive proteins, such as fibronectin (FN) and laminin (LN), provide significant cues to the differentiation into neuronal lineage of mesenchymal stem cells (MSCs) derived from rat bone marrow. When cultured within either a three-dimensional collagen gel alone or one containing either FN or LN, and free of nerve growth factor (NGF), the MSCs showed the development of numerous neurite outgrowths. These were, however, not readily observed in two-dimensional culture without the use of NGF. Immunofluorescence staining, western blot and fluorescence-activated cell sorting analyses demonstrated that a large population of cells was positive for NeuN and glial fibrillary acidic protein, which are specific to neuronal cells, when cultured in the three-dimensional collagen gel. The dependence of the neuronal differentiation of MSCs on the adhesive proteins containing three-dimensional gel matrices is considered to be closely related to focal adhesion kinase (FAK) activation through integrin receptor binding, as revealed by an experiment showing no neuronal outgrowth in the FAK-knockdown cells and stimulation of integrin β1 gene. The results provided herein suggest the potential role of three-dimensional collagen-based gel matrices combined with adhesive proteins in the neuronal differentiation of MSCs, even without the use of chemical differentiation factors. Furthermore, these findings suggest that three-dimensional gel matrices might be useful as nerve-regenerative scaffolds.

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