Expression and Function of Pluripotency Genes in Adult Stem Cells

2011 ◽  
pp. 95-112 ◽  
Author(s):  
Antonio Lo Nigro ◽  
Philip Roelandt ◽  
Catherine M. Verfaillie
2021 ◽  
Author(s):  
Hong-Chen Yan ◽  
Yu Sun ◽  
Ming-Yu Zhang ◽  
Shu-Er Zhang ◽  
Jia-Dong Sun ◽  
...  

Abstract Background Skin-derived stem cells (SDSCs) are a class of adult stem cells (ASCs) that have the ability to self-renew and differentiate. The regulation mechanisms involved in the differentiation of ASCs is a hot topic. Porcine models have close similarities to humans and porcine SDSCs (pSDSCs) offer an ideal in vitro model to investigate human ASCs. To date, studies concerning the role of yes-associated protein (YAP) in ASCs are limited, and the mechanism of its influence on self-renewal and differentiation of ASCs remain unclear. In this paper, we explore the link between the transcriptional regulator YAP and the fate of pSDSCs. Results We found that YAP promotes the pluripotent state of pSDSCs by maintaining the high expression of the pluripotency genes Sox2, Oct4. The overexpression of YAP prevented the differentiation of pSDSCs and the depletion of YAP by small interfering RNA (siRNAs) suppressed the self-renewal of pSDSCs. In addition, we found that YAP regulates the fate of pSDSCs through a mechanism related to the Wnt/β-catenin signaling pathway. When an activator of the Wnt/β-catenin signaling pathway, CHIR99021, was added to pSDSCs overexpressing YAP the ability of pSDSCs to differentiate was partially restored. Conversely, when XAV939 an inhibitor of Wnt/β-catenin signaling pathway, was added to YAP knockdown pSDSCs a higher self-renewal ability resulted. Conclusions our results suggested that, YAP and the Wnt/β-catenin signaling pathway interact to regulate the fate of pSDSCs.


2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S518-S518
Author(s):  
Nathalie Kubis ◽  
Yutaka Tomita ◽  
Valérie Planat ◽  
Alexy Tran Dinh ◽  
Yolande Calando ◽  
...  

Hematology ◽  
2002 ◽  
Vol 2002 (1) ◽  
pp. 369-391 ◽  
Author(s):  
Catherine M. Verfaillie ◽  
Martin F. Pera ◽  
Peter M. Lansdorp

Abstract This update discusses what is known regarding embryonic and adult tissue-derived pluripotent stem cells, including the mechanisms underlying self-renewal without senescence, differentiation in multiple cell types both in vitro and in vivo, and future potential clinical uses of such stem cells. In Section I, Dr. Lansdorp reviews the structure and function of telomerase, the enzyme that restores telomeric ends of chromosomes upon cell division, highly present in embryonic stem cells but not adult stem cells. He discusses the structure and function of telomerase and signaling pathways activated by the enzyme, with special emphasis on normal and leukemic hematopoietic stem cells. In Section II, Dr. Pera reviews the present understanding of mammalian pluripotent embryonic stem cells. He discusses the concept of pluripotentiality in its embryonic context, derivation of stem cells from embryonic or fetal tissue, the basic properties of the stem cells, and methods to produce specific types of differentiated cell from stem cells. He examines the potential applications of stem cells in research and medicine and some of the barriers that must be crossed to achieve these goals. In Section III, Dr. Verfaillie reviews the present understanding of pluripotency of adult stem cells. She discusses the concept of stem cell plasticity, a term used to describe the greater potency described by several investigators of adult tissue-derived stem cells, critically reviews the published studies demonstrating stem cell plasticity, and possible mechanisms underlying such plasticity, and examines the possible role of pluripotent adult stem cells in research and medicine.


2021 ◽  
Vol 7 (3) ◽  
pp. 364
Author(s):  
Ya Ren ◽  
Xue Yang ◽  
Zhengjiang Ma ◽  
Xin Sun ◽  
Yuxin Zhang ◽  
...  

Organoids developed from pluripotent stem cells or adult stem cells are three-dimensional cell cultures possessing certain key characteristics of their organ counterparts, and they can mimic certain biological developmental processes of organs in vitro. Therefore, they have promising applications in drug screening, disease modeling, and regenerative repair of tissues and organs. However, the construction of organoids currently faces numerous challenges, such as breakthroughs in scale size, vascularization, better reproducibility, and precise architecture in time and space. Recently, the application of bioprinting has accelerated the process of organoid construction. In this review, we present current bioprinting techniques and the application of bioinks and summarize examples of successful organoid bioprinting. In the future, a multidisciplinary combination of developmental biology, disease pathology, cell biology, and materials science will aid in overcoming the obstacles pertaining to the bioprinting of organoids. The combination of bioprinting and organoids with a focus on structure and function can facilitate further development of real organs.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Weiwei Sun ◽  
Bin Zhang ◽  
Qingli Bie ◽  
Na Ma ◽  
Na Liu ◽  
...  

The biological role of RNA methylation in stem cells has attracted increasing attention. Recent studies have demonstrated that RNA methylation plays a crucial role in self-renewal, differentiation, and tumorigenicity of stem cells. In this review, we focus on the biological role of RNA methylation modifications including N6-methyladenosine, 5-methylcytosine, and uridylation in embryonic stem cells, adult stem cells, induced pluripotent stem cells, and cancer stem cells, so as to provide new insights into the potential innovative treatments of cancer or other complex diseases.


2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Hefei Wang ◽  
Yu Ren ◽  
Xiao Hu ◽  
Min Ma ◽  
Xiao Wang ◽  
...  

The Wnt signaling is critical for pancreatic development and islet function; however, its precise effects on the development and function of the β-cells remain controversial. Here we examined mRNA and protein expression of components of the Wnt signaling throughout the differentiation of islet β-cells from adipose-derived stem cells (ADSCs). After induction, ADSCs expressed markers of β-cells, including the insulin, PDX1, and glucagon genes, and the PDX1, CK19, nestin, insulin, and C-peptide proteins, indicating their successful differentiation. Compared with pancreatic adult stem cells (PASCs), the quantities of insulin, GLUT2, and Irs2 mRNA decreased, whereas Gcg, Gck, and Irs1 mRNA increased. Over time, during differentiation, insulin mRNA and protein expression increased, Gcg and Gck mRNA expression increased, Irs1 mRNA expression decreased and then increased, and Irs2 mRNA increased and then decreased (all P<0.05). The expression of Dvl-2, LRP5, and GSK3β mRNA as well as the Dvl-2, GSK3β, and p-GSK3β proteins also increased (P<0.05). Expression of TCF7L2 (6–10 d) and β-catenin mRNA as well as the β-catenin protein increased but not significantly (P>0.05). Our results indicate that the Wnt signaling is activated during ADSC differentiation into islet β-cells, but there was no obvious enrichment of nonphosphorylated β-catenin protein.


Biology Open ◽  
2021 ◽  
Vol 10 (4) ◽  
Author(s):  
William R. Jeffery ◽  
Špela Gorički

ABSTRACT In the ascidian Ciona intestinalis, basal body parts regenerate distal structures but distal body parts do not replace basal structures. Regeneration involves the activity of adult stem cells in the branchial sac, which proliferate and produce migratory progenitor cells for tissue and organ replacement. Branchial sac-derived stem cells also replenish recycling cells lining the pharyngeal fissures during homeostatic growth. Apoptosis at injury sites occurs early during regeneration and continuously in the pharyngeal fissures during homeostatic growth. Caspase 1 inhibitor, caspase 3 inhibitor, or pan-caspase inhibitor Z-VAD-FMK treatment blocked apoptosis, prevented regeneration, and suppressed branchial sac growth and function. A pharmacological screen and siRNA-mediated gene knockdown indicated that regeneration requires canonical Wnt signaling. Wnt3a protein rescued both caspase-blocked regeneration and branchial sac growth. Inhibition of apoptosis did not affect branchial sac stem cell proliferation but prevented the survival of progenitor cells. After bisection across the mid-body, apoptosis occurred only in the regenerating basal fragments, although both fragments contained a part of the branchial sac, suggesting that apoptosis is unilateral at the wound site and the presence of branchial sac stem cells is insufficient for regeneration. The results suggest that apoptosis-dependent Wnt signaling mediates regeneration and homeostatic growth in Ciona.


Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1485
Author(s):  
Pooja Flora ◽  
Gil Dalal ◽  
Idan Cohen ◽  
Elena Ezhkova

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.


2020 ◽  
Author(s):  
William R. Jeffery ◽  
Spela Goricki

AbstractBody regeneration is unilateral in the ascidian Ciona intestinalis: severed basal body parts can regenerate distal structures, such as the siphons and neural complex, but severed distal body parts do not replace basal structures. Regeneration involves the activity of adult stem cells in vasculature of the branchial sac, which are induced to proliferate and produce migratory progenitor cells for the replacement of missing tissues and organs. Branchial sac-derived stem cells also replenish continuously recycling cells lining the pharyngeal fissures during homeostatic growth. Apoptosis at injury sites is an early and transient event of regeneration and occurs continuously in the pharyngeal fissures during homeostatic growth. Treatment of amputated animals with caspase 1 inhibitor, caspase 3 inhibitor, or the pan-caspase inhibitor Z-VAD-FMK blocked apoptosis, prevented regeneration, and suppressed the growth and function of the branchial sac. A pharmacological screen and inhibitory siRNA treatments indicated that regeneration and homeostatic growth require canonical Wnt signaling. Furthermore, exogenously supplied recombinant Wnt3a protein rescued both caspase-blocked regeneration and normal branchial sac growth. As determined by EdU pulse-chase studies, inhibition of apoptosis did not affect branchial sac stem cell proliferation but instead prevented the survival of progenitor cells. After bisection across the mid-body, apoptosis at the injury site occurred in the regenerating basal fragments, but not in the non-regenerating distal fragments, although both fragments contain a large portion of the branchial sac, suggesting that apoptosis is unilateral at the wound site and the presence of branchial sac stem cells is insufficient for regeneration. The results show that apoptosis-dependent Wnt signaling mediates regeneration and homeostatic growth by promoting progenitor cell survival in Ciona.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Masamichi Koyanagi ◽  
Chang-Hwan Yoon ◽  
Masayoshi Iwasaki ◽  
Jes-Niels Boeckel ◽  
Janina Trauth ◽  
...  

Induced pluripotent cells (iPS) were generated by overexpression of four factors (Oct3/4, Klf4, c-myc and Sox2) in fibroblasts and showed similar characteristic as embryonic stem (ES) cells. In contrast to iPS and ES cells, adult stem cells have a reduced plasticity. Therefore, we investigated whether reconstitution of the four pluripotency genes in adult progenitor cells improves their therapeutic capacity. Circulating mesoangioblasts (cMAB) have been recently identified in peripheral blood and showed distinct marker expression to bone marrow-derived stem cells and endothelial progenitor cells. cMAB are clonally expandable and exhibit high telomerase activity. cMAB expressed the pluripotency genes Oct3/4, KLF4, and c-Myc, whereas Sox2 and another important stemness gene, Nanog was not expressed. Since only Sox2 was absent out of the four pluripotency genes, we hypothesized that Sox2 transduction may be sufficient to induce pluripotency. Sox2 was overexpressed by lentiviral vector. Interestingly, Sox2-tranduced cMAB not only express Sox2 but also re-express the stem cell gene Nanog. Controls confirmed that the constitutively expressed genes, Oct3/4, KLF4, and c-myc, remained present after Sox2 transduction. Sox2-transduced cMAB formed embryoid body-like structures in culture. In order to test whether Sox2-transduced cells may exhibit improved therapeutic potential, we injected Sox2-transduced cMABs into nude mice after acute myocardial infarction. Four weeks after cell therapy with Sox-overexpressing cells, cardiac function was improved compared to mice treated with control cells (LVEDV/weight; 1.34 ± 0.14 vs 1.88 ± 0.02 μl/g, LVEDP; 13.2 ± 1.0 vs 18.7 ± 2.6 mmHg, dp/dt max; 7989 ± 1030 vs 6331 ± 149 mmHg/s, dp/dt min; 6583 ± 683 vs 4792 ± 514 mmHg/s, and Tau; 9.2 ± 0.8 vs 11.6 ± 1.8 ms, respectively). In summary, the complementation of Sox2 in Oct3/4-, Klf4-, and c-myc-expressing cMABs induced Nanog expression and improved the cardiac regeneration capacity of these circulating adult stem cells.


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