Genomic instability in cultured stem cells: associated risks and underlying mechanisms

2011 ◽  
Vol 6 (5) ◽  
pp. 653-662 ◽  
Author(s):  
Andrew L Ross ◽  
Daniel E Leder ◽  
Jonathan Weiss ◽  
Jan Izakovic ◽  
James M Grichnik
Keyword(s):  
Stem Cells ◽  
Genomic Instability ◽  
Underlying Mechanisms

scholarly journals Establishment and Identification of a CiPSC Lineage Reprogrammed from FSP-tdTomato Mouse Embryonic Fibroblasts (MEFs)

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ruiping Chen ◽  
Wenxiu Xie ◽  
Baomei Cai ◽  
Yue Qin ◽  
Chuman Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Small Molecule ◽  
Fluorescent Protein ◽  
Day Treatment ◽  
Tracking System ◽  
Embryonic Stem ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Underlying Mechanisms

Safety issues associated with transcription factors or viruses may be avoided with the use of chemically induced pluripotent stem cells (CiPSCs), thus promoting their clinical application. Previously, we had successfully developed and standardized an induction method using small-molecule compound, with simple operation, uniform induction conditions, and clear constituents. In order to verify that the CiPSCs were indeed reprogrammed from mouse embryonic fibroblasts (MEFs), and further explore the underlying mechanisms, FSP-tdTomato mice were used to construct a fluorescent protein-tracking system of MEFs, for revealing the process of CiPSC reprogramming. CiPSCs were identified by morphological analysis, mRNA, and protein expression of pluripotency genes, as well as teratoma formation experiments. Results showed that after 40-day treatment of tdTomato-MEFs with small-molecule compounds, the cells were presented with prominent nucleoli, high core-to-cytoplasmic ratio, round shape, group and mass arrangement, and high expression of pluripotency gene. These cells could differentiate into three germ layer tissues in vivo. As indicated by the above results, tdTomato-MEFs could be reprogrammed into CiPSCs, a lineage that possesses pluripotency similar to mouse embryonic stem cells (mESCs), with the use of small-molecule compounds. The establishment of CiPSC lineage, tracked by fluorescent protein, would benefit further studies exploring its underlying mechanisms. With continuous expression of fluorescent proteins during cellular differentiation, this cell lineage could be used for tracking CiPSC transplantation and differentiation into functional cells.

scholarly journals PRMT7: A Pivotal Arginine Methyltransferase in Stem Cells and Development

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Bingyuan Wang ◽  
Mingrui Zhang ◽  
Zhiguo Liu ◽  
Yulian Mu ◽  
Kui Li
Keyword(s):  
Stem Cells ◽  
Developmental Delay ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Embryonic Stem ◽  
Arginine Methylation ◽  
Male Reproduction ◽  
Protein Arginine Methyltransferases ◽  
Underlying Mechanisms ◽  
Induced Pluripotent

Protein arginine methylation is a posttranslational modification catalyzed by protein arginine methyltransferases (PRMTs), which play critical roles in many biological processes. To date, nine PRMT family members, namely, PRMT1, 2, 3, 4, 5, 6, 7, 8, and 9, have been identified in mammals. Among them, PRMT7 is a type III PRMT that can only catalyze the formation of monomethylarginine and plays pivotal roles in several kinds of stem cells. It has been reported that PRMT7 is closely associated with embryonic stem cells, induced pluripotent stem cells, muscle stem cells, and human cancer stem cells. PRMT7 deficiency or mutation led to severe developmental delay in mice and humans, which is possibly due to its crucial functions in stem cells. Here, we surveyed and summarized the studies on PRMT7 in stem cells and development in mice and humans and herein provide a discussion of the underlying molecular mechanisms. Furthermore, we also discuss the roles of PRMT7 in cancer, adipogenesis, male reproduction, cellular stress, and cellular senescence, as well as the future perspectives of PRMT7-related studies. Overall, PRMT7 mediates the proliferation and differentiation of stem cells. Deficiency or mutation of PRMT7 causes developmental delay, including defects in skeletal muscle, bone, adipose tissues, neuron, and male reproduction. A better understanding of the roles of PRMT7 in stem cells and development as well as the underlying mechanisms will provide information for the development of strategies for in-depth research of PRMT7 and stem cells as well as their applications in life sciences and medicine.

scholarly journals Shengjing Capsule Improves Spermatogenesis through Upregulating Integrin α6/β1 in the NOA Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jiamin Wang ◽  
Shankun Zhao ◽  
Lianmin Luo ◽  
Yangzhou Liu ◽  
Ermao Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Sperm Quality ◽  
Sperm Count ◽  
Spermatogonial Stem Cells ◽  
Normal Group ◽  
Seminiferous Tubules ◽  
High Dose ◽  
Sprague Dawley ◽  
Underlying Mechanisms ◽  
Almost All

Objective. To evaluate the therapeutic effect of Shengjing capsules on nonobstructive azoospermia (NOA) in the rat model. Methods. Twenty-five male Sprague–Dawley rats were randomly divided into five groups as follows (n=5 per group): normal group, NOA group, and three Shengjing capsule treatment groups (low-dose, medium-dose, and high-dose groups, respectively). HE staining and semen smear were performed to assess sperm quality. The expression levels of PI3K/AKT and integrin α6/β1 were measured by qRT-PCR and western blot analyses. Results. In the NOA group, almost all of the seminiferous tubules were vacuolated with a thin layer of basal compartment containing some spermatogonial stem cells. The counts of sperms in the NOA group were strongly lower than those of the normal group (P=0.0001). The expression of PI3K/AKT and integrin α6/β1 was scarcely expressed in the NOA group. All indexes mentioned above were significantly different from those of the medium- and high-dose groups (P=0.001, all). The sperm count of rats treated with Shengjing capsules was significantly higher than that of the NOA group (P=0.0001). The rats of Shengjing capsule groups had more layers of spermatogonial stem cells and spermatocytes, and some had intracavitary sperms. Conclusions. Shengjing capsules may be a promising therapeutic medicine for NOA. The underlying mechanisms might involve activating SSCs by upregulating the integrin α6/β1 expression via the PI3K/AKT pathway.

scholarly journals Inhibition of Tet1- and Tet2-mediated DNA demethylation promotes immunomodulation of periodontal ligament stem cells

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Tingting Yu ◽  
Dawei Liu ◽  
Ting Zhang ◽  
Yanheng Zhou ◽  
Songtao Shi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Periodontal Ligament ◽  
Fas Ligand ◽  
Immune Therapy ◽  
Wnt Signaling Pathway ◽  
Dna Demethylation ◽  
Periodontal Ligament Stem Cells ◽  
Promising Target ◽  
Immunomodulatory Properties ◽  
Underlying Mechanisms

Abstract Periodontal ligament stem cells (PDLSCs) possess great potential for clinical treatment of immune diseases due to their extensive immunomodulatory properties. However, the underlying mechanisms that govern the immunomodulatory properties of mesenchymal stem cells (MSCs) are still not fully elucidated. Here, we show that member of the Ten-eleven translocation (Tet) family, a group of DNA demethylases, are capable of regulating PDLSC immunomodulatory functions. Tet1 and Tet2 deficiency enhance PDLSC-induced T cell apoptosis and ameliorate the disease phenotype in colitis mice. Mechanistically, we found that downregulation of Tet1 and Tet2 leads to hypermethylation of DKK-1 promoter, leading to the activation of WNT signaling pathway and therefore promoting Fas ligand (FasL) expression, which results in elevated immunomodulatory capacity of PDLSCs. These results reveal a previously unrecognized role of Tet1 and Tet2 in regulating immunomodulation of PDLSCs. This Tet/DKK-1/FasL cascade may serve as a promising target for enhancing PDLSC-based immune therapy.

scholarly journals Genomic instability en route to and from cancer stem cells

Cell Cycle ◽  
2009 ◽  
Vol 8 (7) ◽  
pp. 1000-1002 ◽  
Author(s):  
Linda Li ◽  
Laura Borodyansky ◽  
Youxin Yang
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Genomic Instability

scholarly journals Kinetics of normal hematopoietic stem and progenitor cells in a Notch1-induced leukemia model

Blood ◽  
2009 ◽  
Vol 114 (18) ◽  
pp. 3783-3792 ◽  
Author(s):  
Xiaoxia Hu ◽  
Hongmei Shen ◽  
Chen Tian ◽  
Hui Yu ◽  
Guoguang Zheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Progenitor Cells ◽  
Quiescent State ◽  
Hematopoietic Stem ◽  
Definitive Evidence ◽  
Accelerated Proliferation ◽  
Stem And Progenitor Cells ◽  
Underlying Mechanisms ◽  
The Impact

Abstract The predominant outgrowth of malignant cells over their normal counterparts in a given tissue is a shared feature for all types of cancer. However, the impact of a cancer environment on normal tissue stem and progenitor cells has not been thoroughly investigated. We began to address this important issue by studying the kinetics and functions of hematopoietic stem and progenitor cells in mice with Notch1-induced leukemia. Although hematopoiesis was progressively suppressed during leukemia development, the leukemic environment imposed distinct effects on hematopoietic stem and progenitor cells, thereby resulting in different outcomes. The normal hematopoietic stem cells in leukemic mice were kept in a more quiescent state but remained highly functional on transplantation to nonleukemic recipients. In contrast, the normal hematopoietic progenitor cells in leukemic mice demonstrated accelerated proliferation and exhaustion. Subsequent analyses on multiple cell-cycle parameters and known regulators (such as p21, p27, and p18) further support this paradigm. Therefore, our current study provides definitive evidence and plausible underlying mechanisms for hematopoietic disruption but reversible inhibition of normal hematopoietic stem cells in a leukemic environment. It may also have important implications for cancer prevention and treatment in general.

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