Non-Coding RNAs in Stem Cell Regulation and Cardiac Regeneration: Current Problems and Future Perspectives

Although advances in rapid revascularization strategies following acute myocardial infarction (AMI) have led to improved short and long-term outcomes, the associated loss of cardiomyocytes and the subsequent remodeling result in an impaired ventricular function that can lead to heart failure or death. The poor regenerative capacity of the myocardium and the current lack of effective regenerative therapies have driven stem cell research in search of a possible solution. One approach involves the delivery of stem cells to the site of injury in order to stimulate repair response. Although animal studies initially delivered promising results, the application of similar techniques in humans has been hampered by poor target site retention and oncogenic considerations. In response, several alternative strategies, including the use of non-coding RNAs (ncRNAs), have been introduced with the aim of activating and regulating stem cells or inducing stem cell status in resident cells. Circular RNAs (circRNAs) and microRNAs (miRNAs) are ncRNAs with pivotal functions in cell proliferation and differentiation, whose role in stem cell regulation and potential significance for the field of cardiac regeneration is the primary focus of this review. We also address the general advantages of ncRNAs as promising drivers of cardiac regeneration and potent stem cell regulators.

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Two anatomically distinct niches regulate stem cell activity

Blood ◽

10.1182/blood-2012-04-424507 ◽

2012 ◽

Vol 120 (11) ◽

pp. 2174-2181 ◽

Cited By ~ 53

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.

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Fundamental mechanisms of the stem cell regulation in land plants: lesson from shoot apical cells in bryophytes

Plant Molecular Biology ◽

10.1007/s11103-021-01126-y ◽

2021 ◽

Author(s):

Yuki Hata ◽

Junko Kyozuka

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Molecular Mechanisms ◽

Cell Function ◽

Chromatin Modification ◽

Land Plants ◽

Marchantia Polymorpha ◽

Cell Regulation ◽

Evolutionary Trajectory ◽

Stem Cell Regulation

Abstract Key message This review compares the molecular mechanisms of stem cell control in the shoot apical meristems of mosses and angiosperms and reveals the conserved features and evolution of plant stem cells. Abstract The establishment and maintenance of pluripotent stem cells in the shoot apical meristem (SAM) are key developmental processes in land plants including the most basal, bryophytes. Bryophytes, such as Physcomitrium (Physcomitrella) patens and Marchantia polymorpha, are emerging as attractive model species to study the conserved features and evolutionary processes in the mechanisms controlling stem cells. Recent studies using these model bryophyte species have started to uncover the similarities and differences in stem cell regulation between bryophytes and angiosperms. In this review, we summarize findings on stem cell function and its regulation focusing on different aspects including hormonal, genetic, and epigenetic control. Stem cell regulation through auxin, cytokinin, CLAVATA3/EMBRYO SURROUNDING REGION-RELATED (CLE) signaling and chromatin modification by Polycomb Repressive Complex 2 (PRC2) and PRC1 is well conserved. Several transcription factors crucial for SAM regulation in angiosperms are not involved in the regulation of the SAM in mosses, but similarities also exist. These findings provide insights into the evolutionary trajectory of the SAM and the fundamental mechanisms involved in stem cell regulation that are conserved across land plants.

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Predicting gene regulatory networks by combining spatial and temporal gene expression data in Arabidopsis root stem cells

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1707566114 ◽

2017 ◽

Vol 114 (36) ◽

pp. E7632-E7640 ◽

Cited By ~ 41

Author(s):

Maria Angels de Luis Balaguer ◽

Adam P. Fisher ◽

Natalie M. Clark ◽

Maria Guadalupe Fernandez-Espinosa ◽

Barbara K. Möller ◽

...

Keyword(s):

Mathematical Modeling ◽

Stem Cells ◽

Stem Cell ◽

Regulatory Networks ◽

Network Inference ◽

Quiescent Center ◽

Cell Regulation ◽

Gene Regulatory Network Inference ◽

Stem Cell Regulation ◽

Gene Regulatory

Identifying the transcription factors (TFs) and associated networks involved in stem cell regulation is essential for understanding the initiation and growth of plant tissues and organs. Although many TFs have been shown to have a role in the Arabidopsis root stem cells, a comprehensive view of the transcriptional signature of the stem cells is lacking. In this work, we used spatial and temporal transcriptomic data to predict interactions among the genes involved in stem cell regulation. To accomplish this, we transcriptionally profiled several stem cell populations and developed a gene regulatory network inference algorithm that combines clustering with dynamic Bayesian network inference. We leveraged the topology of our networks to infer potential major regulators. Specifically, through mathematical modeling and experimental validation, we identified PERIANTHIA (PAN) as an important molecular regulator of quiescent center function. The results presented in this work show that our combination of molecular biology, computational biology, and mathematical modeling is an efficient approach to identify candidate factors that function in the stem cells.

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Glycans in stem cell regulation: from Drosophila tissue stem cells to mammalian pluripotent stem cells

FEBS Letters ◽

10.1002/1873-3468.13167 ◽

2018 ◽

Vol 592 (23) ◽

pp. 3773-3790 ◽

Cited By ~ 8

Author(s):

Shoko Nishihara

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Pluripotent Stem Cells ◽

Cell Regulation ◽

Stem Cell Regulation

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

Development ◽

10.1242/dev.191924 ◽

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.

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An inference approach combines spatial and temporal gene expression data to predict gene regulatory networks in Arabidopsis stem cells

10.1101/140269 ◽

2017 ◽

Cited By ~ 2

Author(s):

Maria Angels de Luis Balaguer ◽

Adam P. Fisher ◽

Natalie M. Clark ◽

Maria Guadalupe Fernandez-Espinosa ◽

Barbara K. Möller ◽

...

Keyword(s):

Mathematical Modeling ◽

Stem Cells ◽

Stem Cell ◽

Regulatory Networks ◽

Dynamic Bayesian Network ◽

Quiescent Center ◽

Cell Regulation ◽

Stem Cell Regulation ◽

Transcriptional Signature ◽

Gene Regulatory

AbstractIdentifying the transcription factors (TFs) and associated networks involved in stem cell regulation is key for understanding the initiation and growth of plant tissues and organs. Although many TFs have been shown to have a role in the Arabidopsis root stem cells, a comprehensive view of the transcriptional signature of the stem cells is lacking. In this work, we used spatial and temporal transcriptomic data to predict interactions among the genes involved in stem cell regulation. For this, we transcriptionally profiled several stem cell populations and developed a gene regulatory network (GRN) inference algorithm that combines clustering with Dynamic Bayesian Network (DBN) inference. We leveraged the topology of our networks to infer potential key regulators. The results presented in this work show that our combination of molecular biology approaches, computational biology and mathematical modeling was key to identify candidate factors that function in the stem cells. Specifically, through experimental validation and mathematical modeling, we identified PERIANTHIA (PAN) as an important molecular regulator of quiescent center (QC) function.

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The physiological basis of intracrine stem cell regulation

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00461.2008 ◽

2008 ◽

Vol 295 (2) ◽

pp. H447-H453 ◽

Cited By ~ 12

Author(s):

Richard N. Re ◽

Julia L. Cook

Keyword(s):

Stem Cells ◽

Stem Cell ◽

High Mobility ◽

Feedback Loops ◽

Cell Regulation ◽

High Mobility Group Protein ◽

Physiological Basis ◽

Stem Cell Regulation ◽

Group Protein

Intracrine peptides and proteins participate in the regulation of adult and pleuripotential embryonic-like stem cells. Included among these factors are VEGF, dynorphin, the readthrough form of acetylcholinesterase, Oct3/4, Pdx-1, Pax-6, and high-mobility group protein B1, among others. In some cases, the establishment of intracrine feedback loops can be shown to be relevant to this regulation, consistent with previously proposed principles of intracrine action. Here the role of intracrines in stem cell regulation is reviewed, with particular attention to the intracrine regulation of cardiac stem cells. The reprogramming of cells to restore the pleuripotent phenotype and the possible role of stem/progenitor cells in neoplasia are also discussed.

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