scholarly journals Two anatomically distinct niches regulate stem cell activity

Blood ◽  
2012 ◽  
Vol 120 (11) ◽  
pp. 2174-2181 ◽  
Author(s):  
Hideo Ema ◽  
Toshio Suda
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Cell Activity ◽  
Cell Types ◽  
Cell Number ◽  
Cell Regulation ◽  
Hematopoietic Stem ◽  
Stem Cell Regulation ◽  
Cellular Components

Abstract The niche microenvironment controls stem cell number, fate, and behavior. The bone marrow, intestine, and skin are organs with highly regenerative potential, and all produce a large number of mature cells daily. Here, focusing on adult stem cells in these organs, we compare the structures and cellular components of their niches and the factors they produce. We then define the niche as a functional unit for stem cell regulation. For example, the niche possibly maintains quiescence and regulates fate in stem cells. Moreover, we discuss our hypothesis that many stem cell types are regulated by both specialized and nonspecialized niches, although hematopoietic stem cells, as an exception, are regulated by a nonspecialized niche only. The specialized niche is composed of 1 or a few types of cells lying on the basement membrane in the epithelium. The nonspecialized niche is composed of various types of cells widely distributed in mesenchymal tissues. We propose that the specialized niche plays a role in local regulation of stem cells, whereas the nonspecialized niche plays a role in relatively broad regional or systemic regulation. Further work will verify this dual-niche model to understand mechanisms underlying stem cell regulation.

scholarly journals Lipid metabolism in focus: how the build-up and breakdown of lipids affects stem cells

Development ◽  
2021 ◽  
Vol 148 (10) ◽  
Author(s):  
Sofia Madsen ◽  
Mergim Ramosaj ◽  
Marlen Knobloch
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Lipid Metabolism ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Cell Regulation ◽  
Beta Oxidation ◽  
Hematopoietic Stem ◽  
Stem Cell Regulation ◽  
Neural Stem Progenitor Cells

ABSTRACT Cellular metabolism has recently emerged as a key regulator of stem cell behavior. Various studies have suggested that metabolic regulatory mechanisms are conserved in different stem cell niches, suggesting a common level of stem cell regulation across tissues. Although the balance between glycolysis and oxidative phosphorylation has been shown to be distinct in stem cells and their differentiated progeny, much less is known about lipid metabolism in stem cell regulation. In this Review, we focus on how stem cells are affected by two major lipid metabolic pathways: the build-up of lipids, called de novo lipogenesis, and the breakdown of lipids, called fatty acid beta-oxidation. We cover the recent literature on hematopoietic stem cells, intestinal stem cells, neural stem/progenitor cells and cancer stem cells, where these two lipid pathways have been studied in more depth.

scholarly journals Multiple Roles for Cholinergic Signaling from the Perspective of Stem Cell Function

2021 ◽  
Vol 22 (2) ◽  
pp. 666
Author(s):  
Toshio Takahashi
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Function ◽  
Cell Activity ◽  
Embryonic Stem ◽  
Cholinergic Neurons ◽  
Cell Types ◽  
Proliferative Potential ◽  
True Nature ◽  
Cholinergic Signaling

Stem cells have extensive proliferative potential and the ability to differentiate into one or more mature cell types. The mechanisms by which stem cells accomplish self-renewal provide fundamental insight into the origin and design of multicellular organisms. These pathways allow the repair of damage and extend organismal life beyond that of component cells, and they probably preceded the evolution of complex metazoans. Understanding the true nature of stem cells can only come from discovering how they are regulated. The concept that stem cells are controlled by particular microenvironments, also known as niches, has been widely accepted. Technical advances now allow characterization of the zones that maintain and control stem cell activity in several organs, including the brain, skin, and gut. Cholinergic neurons release acetylcholine (ACh) that mediates chemical transmission via ACh receptors such as nicotinic and muscarinic receptors. Although the cholinergic system is composed of organized nerve cells, the system is also involved in mammalian non-neuronal cells, including stem cells, embryonic stem cells, epithelial cells, and endothelial cells. Thus, cholinergic signaling plays a pivotal role in controlling their behaviors. Studies regarding this signal are beginning to unify our understanding of stem cell regulation at the cellular and molecular levels, and they are expected to advance efforts to control stem cells therapeutically. The present article reviews recent findings about cholinergic signaling that is essential to control stem cell function in a cholinergic niche.

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 Genetic control of the frequency of hematopoietic stem cells in mice: mapping of a candidate locus to chromosome 1.

1996 ◽  
Vol 183 (3) ◽  
pp. 1141-1150 ◽  
Author(s):  
C E Müller-Sieburg ◽  
R Riblet
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Inbred Strains ◽  
Cell Number ◽  
Chromosome 1 ◽  
Cell Frequency ◽  
Candidate Locus ◽  
Hematopoietic Stem ◽  
Differentiation And Proliferation

The genetic elements that govern the differentiation and proliferation of hematopoietic stem cells remain to be defined. We describe here marked strain-specific differences in the frequency of long-term culture-initiating cells (LTC-IC) in the bone marrow of different strains of mice. Mice of C57Bl/6 background showed the lowest levels of stem cells in marrow, averaging 2.4 +/- .06 LTC-IC/10(5) cells, BALB/c is intermediate (9.1 +/- 4.2/10(5) cells), and DBA/2 mice contained a 11-fold higher frequency of LTC-IC (28.1 +/- 16.5/10(5) cells) than C57Bl/6 mice. The genetic factors affecting the size of the stem cell pool were analyzed in the C57Bl/6 X DBA/2 recombinant inbred strains; LTC-IC frequencies ranged widely, indicating that stem cell frequencies are controlled by multiple genes. Quantitative trait linkage analysis suggested that two loci that have major quantitative effects are located on chromosome 1 near Adprp and Acrg, respectively. The mapping of the locus near Adprp was confirmed by finding an elevated stem cell frequency in B6.C-H25, a C57Bl/6 congenic strain that carries a portion of chromosome 1 derived from BALB/c mice. We have named this gene Scfr1 (stem cell frequency regulator 1). The allelic forms of this gene may be an important predictor of stem cell number and thus would be useful for evaluating cell sources in clinical stem cell transplantation.

Types of Stem Cells Used in US-Based Clinical Trials between 1999 and 2014

2021 ◽  
Vol 26 ◽  
pp. 169-191
Author(s):  
Emma E. Redfield ◽  
Erin K. Luciano ◽  
Monica J. Sewell ◽  
Lucas A. Mitzel ◽  
Isaac J. Sanford ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
The Us ◽  
Health Database ◽  
Induced Pluripotent

This study looks at the number of clinical trials involving specific stem cell types. To our knowledge, this has never been done before. Stem cell clinical trials that were conducted at locations in the US and registered on the National Institutes of Health database at ‘clinicaltrials.gov’ were categorized according to the type of stem cell used (adult, cancer, embryonic, perinatal, or induced pluripotent) and the year that the trial was registered. From 1999 to 2014, there were 2,357 US stem cell clinical trials registered on ‘clinicaltrials.gov,’ and 89 percent were from adult stem cells and only 0.12 percent were from embryonic stem cells. This study concludes that embryonic stem cells should no longer be used for clinical study because of their irrelevance, moral questions, and induced pluripotent stem cells.

scholarly journals Regulation of Prostatic Stem Cells by Stromal Niche in Health and Disease

Endocrinology ◽  
2008 ◽  
Vol 149 (9) ◽  
pp. 4303-4306 ◽  
Author(s):  
Gail P. Risbridger ◽  
Renea A. Taylor
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Tumor Stroma ◽  
Stem Cell Differentiation ◽  
Stem Cell Regulation ◽  
Isolation And Characterization ◽  
Tissue Recombination ◽  
Cell Niche

The isolation and characterization of prostatic stem cells has received significant attention in the last few years based on the belief that aberrant regulation of adult stem cells leads to prostate disease including cancer. The nature of the perturbations in stem cell regulation remains largely unknown. Although adult stem cells are can be governed by autonomous regulatory mechanisms, the stromal niche environment also provides essential cues to direct directing differentiation decisions and can lead to aberrant proliferation and/or differentiation. Elegant tissue recombination experiments, pioneered by Gerald Cunha and colleagues, provided evidence that quiescent epithelial tissues containing adult stem cells were capable of altered differentiation in response to inductive and instructive mesenchyme. In more recent times, it has been demonstrated that embryonic mesenchyme is sufficiently powerful to direct the differentiation of embryonic stem cells into mature prostate or bladder. In addition, prostatic tumor stroma provides another unique niche or microenvironment for stem cell differentiation that is distinct to normal stroma. This review highlights the importance of the appropriate selection of the stromal cell niche for tissue regeneration and implies plasticity of adult stem cells that is dictated by the tissue microenvironment.

Human hematopoietic stem cells stimulated to proliferate in vitro lose engraftment potential during their S/G2/M transit and do not reenter G0

Blood ◽  
2000 ◽  
Vol 96 (13) ◽  
pp. 4185-4193 ◽  
Author(s):  
Hanno Glimm ◽  
IL-Hoan Oh ◽  
Connie J. Eaves
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Cell Activity ◽  
Human Cord Blood ◽  
Hematopoietic Stem ◽  
A Cell

Abstract An understanding of mechanisms regulating hematopoietic stem cell engraftment is of pivotal importance to the clinical use of cultured and genetically modified transplants. Human cord blood (CB) cells with lymphomyeloid repopulating activity in NOD/SCID mice were recently shown to undergo multiple self-renewal divisions within 6 days in serum-free cultures containing Flt3-ligand, Steel factor, interleukin 3 (IL-3), IL-6, and granulocyte colony-stimulating factor. The present study shows that, on the fifth day, the transplantable stem cell activity is restricted to the G1fraction, even though both colony-forming cells (CFCs) and long-term culture-initiating cells (LTC-ICs) in the same cultures are approximately equally distributed between G0/G1and S/G2/M. Interestingly, the G0 cells defined by their low levels of Hoechst 33342 and Pyronin Y staining, and reduced Ki67 and cyclin D expression (representing 21% of the cultured CB population) include some mature erythroid CFCs but very few primitive CFCs, LTC-ICs, or repopulating cells. Although these findings suggest a cell cycle–associated change in in vivo stem cell homing, the cultured G0/G1 and S/G2/M CD34+ CB cells exhibited no differences in levels of expression of VLA-4, VLA-5, or CXCR-4. Moreover, further incubation of these cells for 1 day in the presence of a concentration of transforming growth factor β1 that increased the G0/G1 fraction did not enhance detection of repopulating cells. The demonstration of a cell cycle–associated mechanism that selectively silences the transplantability of proliferating human hematopoietic stem cells poses both challenges and opportunities for the future improvement of ex vivo–manipulated grafts.

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