Abstract 160: Pim-1 Preserves Cardiac Stem Cell Proliferation with Age

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Michael McGregor ◽  
Shabana Din ◽  
Natalie Gude ◽  
Mark A Sussman
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Time Course ◽  
Protein A ◽  
Cell Types ◽  
Tissue Homeostasis ◽  
Dominant Negative ◽  
Repair Capacity ◽  
Tissue Samples ◽  
The Impact

Rationale Cardiac stem cells (CSC) regulate cardiomyogenesis and support regenerative processes in the heart, but aging adversely affects stem cell repair capacity. Aging is a primary cause of impaired cardiac function characterized by accumulation of senescent cells. CSC senescence is associated with permanent growth arrest that decreases survival signaling and cellular replacement, inevitably diminishing the capacity of the heart to maintain tissue homeostasis. Therefore, promoting CSC growth may improve cardiac performance with age. Pim-1 kinase exhibits protective and proliferative effects in the myocardium but the role of Pim-1 in cardiac aging has not been thoroughly studied. Objective Demonstrate that Pim-1 promotes stem cell growth in the aged myocardium correlating with increased expression of centromere protein A (CENP-A), a kinetochore-associated protein known to support cell proliferation in numerous species and cell types. Methods & Results CENP-A expression levels were evaluated from murine myocardial tissue samples ranging in age from 11 days post coitum to 4 months of age with analysis by immunoblot as well as quantitative PCR. CENP-A expression was colocalized with c-kit as a marker of CSC by immunohistochemical labeling, revealing a decline in CENP-A expression over the time course of postnatal myocardial maturation. The impact of Pim-1 upon CENP-A level was assessed by comparative analysis of non-transgenic mice versus genetically modified transgenic mouse lines expressing either Pim-1 (wild type) or a dominant negative functionally dead Pim-1 mutant. Pim-1 overexpression increases persistence of CENP-A in CSCs with age, as well as the prevalence of cycling CSCs as marked by phosph-H3 expression, while the functionally dead mutant accelerates CENP-A diminution and decreases CSC proliferation. Conclusion CENP-A decline in c-kit positive cells with age provides intriguing evidence of a potential mechanism for the diminished capacity of CSCs to maintain tissue homeostasis. Pim-1 mitigates CENP-A diminution, demonstrating the promising potential of Pim-1 to promote cardiac growth and repair with age.

Deterministic Trigger of Self-Renewal in Expanded HSCs Expressing Hoxb4 + Antisense Pbx1.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 800-800
Author(s):  
Sonia Cellot ◽  
Jana Krosl ◽  
Keith Humphries ◽  
Guy Sauvageau
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Cell Fate ◽  
Time Course ◽  
Cell Cycle Distribution ◽  
Self Renewal ◽  
Primary Mouse ◽  
The Impact

Abstract We previously reported the generation of pluripotent and ultracompetitive HSCs through modulation of Hoxb4 and Pbx1 levels. These Hoxb4hiPbx1lo HSCs display a tremendous regenerative potential, yet they are still fully responsive to in vivo regulatory signals that control stem cell pool size (20 000 HSCmouse) and differentiation pathways. Further work in our laboratory attempted to circumvent these physiological constraints by expanding Hoxb4hiPbx1lo transduced HSCs in vitro, and hence revealing their intrinsic expansion potential. Independent experiments were performed where primary mouse BM cells were co-infected with retroviruses encoding antisense Pbx1 cDNA plus YFP, and Hoxb4 plus GFP (double gene transfer ranged between 20–50%). Hoxb4hiPbx1lo HSCs measured using the CRU assay expanded by 105-fold during a 12 day in vitro culture. Following serial transplantations, these cells displayed an additional 4–5 log expansion in vivo. Total stem cell content per animal remained within normal limits. Southern blot analyses of proviral integrations showed that the expansion was polyclonal, and analyses of individually expanded clones provided a molecular proof of in vitro self-renewal (SR). This unprecedented level of HSC expansion in such a short time course (105-fold in 12 days) implies an absolute HSC doubling time of approximately 17 hours in our culture, raising the possibility that virtually all dividing HSCs undergo self-renewal. This analysis prompted us to dissect the impact of Hoxb4 on cell proliferation versus cell fate (SR?). When analyzed during the period of maximal HSC expansion, the cell cycle distribution of Sca+ or Sca+Lin− cells were comparable between the cultures initiated with neo control versus Hoxb4 BM cells (CTL vs Hoxb4: G0/G1: 66% vs 83%; S: 15% vs 9%; G2/M: 18% vs 7%). Correspondingly, CFSE tracking studies confirmed the identical, or even lower, number of cellular divisions in Sca+ cells isolated from cultures initiated with Hoxb4 versus neo transduced cells. Annexin V studies precluded protection from apoptosis as the major mechanism to increase HSC numbers since similar results (3–10% positive cells) were observed in the Hoxb4 versus neo-transduced cells. In summary, our studies support the emerging concept that distinct molecular pathways regulate cell proliferation and self-renewal, suggesting that Hoxb4 + antisense Pbx1 predominantly triggers self-renewal over HSC proliferation.

scholarly journals The impact of ageing on lipid-mediated regulation of adult stem cell behavior and tissue homeostasis

2020 ◽  
Vol 189 ◽  
pp. 111278
Author(s):  
Rafael Sênos Demarco ◽  
Marie Clémot ◽  
D. Leanne Jones
Keyword(s):  
Stem Cell ◽  
Adult Stem Cell ◽  
Tissue Homeostasis ◽  
Cell Behavior ◽  
The Impact

scholarly journals Mitofusin-2: A New Mediator of Pathological Cell Proliferation

2021 ◽  
Vol 9 ◽  
Author(s):  
Yanguo Xin ◽  
Junli Li ◽  
Wenchao Wu ◽  
Xiaojing Liu
Keyword(s):  
Cell Proliferation ◽  
Potential Role ◽  
Mitochondrial Dynamics ◽  
Cell Types ◽  
Tissue Homeostasis ◽  
Mitochondrial Network ◽  
Biological Functions ◽  
Potential Therapeutic Target ◽  
Mitofusin 2 ◽  
Growing Body

Cell proliferation is an important cellular process for physiological tissue homeostasis and remodeling. The mechanisms of cell proliferation in response to pathological stresses are not fully understood. Mitochondria are highly dynamic organelles whose shape, number, and biological functions are modulated by mitochondrial dynamics, including fusion and fission. Mitofusin-2 (Mfn-2) is an essential GTPase-related mitochondrial dynamics protein for maintaining mitochondrial network and bioenergetics. A growing body of evidence indicates that Mfn-2 has a potential role in regulating cell proliferation in various cell types. Here we review these new functions of Mfn-2, highlighting its crucial role in several signaling pathways during the process of pathological cell proliferation. We conclude that Mfn-2 could be a new mediator of pathological cell proliferation and a potential therapeutic target.

scholarly journals New Insights into the Role of Epithelial–Mesenchymal Transition during Aging

2019 ◽  
Vol 20 (4) ◽  
pp. 891 ◽  
Author(s):  
Francisco Santos ◽  
Cristiana Moreira ◽  
Sandrina Nóbrega-Pereira ◽  
Bruno Bernardes de Jesus
Keyword(s):  
Stem Cell ◽  
Aging Process ◽  
Cell Function ◽  
Epithelial Mesenchymal Transition ◽  
Normal Aging ◽  
Tissue Homeostasis ◽  
Mesenchymal Transition ◽  
The Impact ◽  
Possible Cause

Epithelial–mesenchymal transition (EMT) is a cellular process by which differentiated epithelial cells undergo a phenotypic conversion to a mesenchymal nature. The EMT has been increasingly recognized as an essential process for tissue fibrogenesis during disease and normal aging. Higher levels of EMT proteins in aged tissues support the involvement of EMT as a possible cause and/or consequence of the aging process. Here, we will highlight the existing understanding of EMT supporting the phenotypical alterations that occur during normal aging or pathogenesis, covering the impact of EMT deregulation in tissue homeostasis and stem cell function.

scholarly journals Cell proliferation induced by modified cationic dextran

2018 ◽  
Vol 14 (4) ◽  
Author(s):  
Kamil Kamiński ◽  
Krystyna Stalińska ◽  
Anna Niziołek ◽  
Maria Wróbel ◽  
Maria Nowakowska ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Positive Impact ◽  
Cell Aggregation ◽  
Fibroblast Cell ◽  
Cell Types ◽  
Cationic Modification ◽  
Diphenyl Tetrazolium Bromide ◽  
The Impact

Abstract The interaction between oppositely charged membranes and polycations causes cell aggregation, loss of membrane fluidity, and membrane degeneration and may cause an increase of its permeability. Unfortunately, the interaction is the reason why the use of polycations in medicine is severely limited. Therefore, in this paper, we share our observations related to the action of 40-kDa dextran modified using glycidyltrimethylammonium chloride, resulting in increased fibroblast cell proliferation. Using viability and proliferation tests [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, crystal violet, 3H-thymidine incorporation], we have observed that cationic dextran derivatives exert a positive impact on nonepithelial cell proliferation in vitro. This phenomenon has been noted for human and mouse fibroblasts and several other nonepithelial cell lines. However, the effect seems to be most pronounced for fibroblast cell lines. The presented studies allow to examine the impact of the polymer structure and the methods of its cationic modification on this newly observed phenomenon. The observation is unique because positively charged macromolecules usually exhibit high toxicity in all cell types in vitro.

scholarly journals Roles of Melatonin in Goat Hair Follicle Stem Cell Proliferation and Pluripotency Through Regulating the Wnt Signaling Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Weidong Zhang ◽  
Niu Wang ◽  
Tongtong Zhang ◽  
Meng Wang ◽  
Wei Ge ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Wnt Signaling ◽  
Hair Follicle ◽  
Wnt Signaling Pathway ◽  
Hematopoietic Progenitor Cell ◽  
Hair Follicle Stem Cells ◽  
Follicle Stem Cells ◽  
The Impact

Emerging studies show that melatonin promotes cashmere development through hypodermic implantation. However, the impact and underlying mechanisms are currently unknown. In vitro study has previously demonstrated that melatonin induces cashmere growth by regulating the proliferation of goat secondary hair follicle stem cells (gsHFSCs), but there is limited information concerning the effects of melatonin on cell pluripotency. It is also known that Wnt signaling may actively participate in regulating cell proliferation and stem cell pluripotency. Therefore, in the current investigation, goat hair follicle stem cells were exposed to multiple concentrations of melatonin and different culture times to reveal the relationship between melatonin and the activation of Wnt signaling. A proportionally high Catenin beta-1 (CTNNB1) response was induced by 500 ng/L of melatonin, but it was then suppressed with the dosages over 1,000 ng/L. Greater amounts of CTNNB1 entered the cell nuclei by extending the exposure time to 72 h, which activated transcription factor 4/lymphoid enhancer-binding factor 1 and promoted the expression of the proliferation-related genes C-MYC, C-JUN, and CYCLIND1. Moreover, nuclear receptor ROR-alpha (RORα) and bone morphogenetic protein 4 (BMP4) were employed to analyze the underlying mechanism. RORα presented a sluggish concentration/time-dependent rise, but BMP4 was increased dramatically by melatonin exposure, which revealed that melatonin might participate in regulating the pluripotency of hair follicle stem cells. Interestingly, NOGGIN, which is a BMP antagonist and highly relevant to cell stemness, was also stimulated by melatonin. These findings demonstrated that melatonin exposure and/or NOGGIN overexpression in hair follicle stem cells might promote the expression of pluripotency markers Homeobox protein NANOG, Organic cation/carnitine transporter 4, and Hematopoietic progenitor cell antigen CD34. Our findings here provided a comprehensive view of Wnt signaling in melatonin stimulated cells and melatonin mediated stemness of gsHFSCs by regulating NOGGIN, which demonstrates a regulatory mechanism of melatonin enhancement on the growth of cashmere.

scholarly journals The Impact of NLRP3 Activation on Hematopoietic Stem Cell Transplantation

2021 ◽  
Vol 22 (21) ◽  
pp. 11845
Author(s):  
J. Luis Espinoza ◽  
Kosuke Kamio ◽  
Vu Quang Lam ◽  
Akiyoshi Takami
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cell Types ◽  
Hematopoietic Stem ◽  
Hematological Disorders ◽  
The Impact ◽  
Transplant Complications

NLR family pyrin domain-containing 3 (NLRP3) is an intracellular protein that after recognizing a broad spectrum of stressors, such as microbial motifs and endogenous danger signals, promotes the activation and release of the pro-inflammatory cytokines IL-1β and IL-18, thus playing an essential role in the innate immune response. Several blood cell types, including macrophages, dendritic cells, and hematopoietic stem and progenitor cells (HSPCs), express NLRP3, where it has been implicated in various physiological and pathological processes. For example, NLRP3 participates in the development and expansion of HSPCs, and their release from bone marrow into the peripheral blood has been implicated in certain hematological disorders including various types of leukemia. In addition, accumulating evidence indicates that activation of NLRP3 plays a pivotal role in the development of transplant complications in patients receiving hematopoietic stem cell transplantation (HSCT) including graft versus host disease, severe infections, and transplant-related mortality. The majority of these complications are triggered by the severe tissue damage derived from the conditioning regimens utilized in HSCT which, in turn, activates NLRP3 and, ultimately, promotes the release of proinflammatory cytokines such as IL-1β and IL-18. Here, we summarize the implications of NLRP3 in HSCT with an emphasis on the involvement of this inflammasome component in transplant complications.

scholarly journals A Computational Model of Stem Cell Molecular Mechanism to Maintain Tissue Homeostasis

2020 ◽  
Author(s):  
Najme Khorasani ◽  
Mehdi Sadeghi ◽  
Abbas Nowzari-Dalini
Keyword(s):  
Decision Making ◽  
Stem Cells ◽  
Stem Cell ◽  
Computational Model ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Tissue Homeostasis ◽  
Short Period ◽  
Dynamic Stochastic ◽  
The Impact

Stem cells, with their capacity to self-renew and to differentiate to more specialized cell types, play a key role to maintain homeostasis in adult tissues. To investigate how, in the dynamic stochastic environment of a tissue, non-genetic diversity and the precise balance between proliferation and differentiation are achieved, it is necessary to understand the molecular mechanisms of the stem cells in decision making process. By focusing on the impact of stochasticity, we proposed a computational model describing the regulatory circuitry as a tri-stable dynamical system to reveal the mechanism which orchestrate this balance. Our model explains how the distribution of noise in genes, linked to the cell regulatory networks, controls cell decision-making to maintain homeostatic state. The noise control over tissue homeostasis is achieved by regulating the probability of differentiation and self-renewal through symmetric and/or asymmetric cell divisions. Our model reveals, when mutations due to the replication of DNA in stem cell division, are inevitable, how mutations contribute to either aging gradually or the development of cancer in a short period of time. Furthermore, our model sheds some light on the impact of more complex regulatory networks on the system robustness against perturbations.

scholarly journals The Impact of Metallic Nanoparticles on Stem Cell Proliferation and Differentiation

Nanomaterials ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. 761 ◽  
Author(s):  
Ahmed Abdal Dayem ◽  
Soo Lee ◽  
Ssang-Goo Cho
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Metallic Nanoparticles ◽  
Stem Cell Differentiation ◽  
Stem Cell Proliferation ◽  
Cell Functions ◽  
Cell Proliferation And Differentiation ◽  
Wide Range ◽  
Proliferation And Differentiation ◽  
The Impact

Nanotechnology has a wide range of medical and industrial applications. The impact of metallic nanoparticles (NPs) on the proliferation and differentiation of normal, cancer, and stem cells is well-studied. The preparation of NPs, along with their physicochemical properties, is related to their biological function. Interestingly, various mechanisms are implicated in metallic NP-induced cellular proliferation and differentiation, such as modulation of signaling pathways, generation of reactive oxygen species, and regulation of various transcription factors. In this review, we will shed light on the biomedical application of metallic NPs and the interaction between NPs and the cellular components. The in vitro and in vivo influence of metallic NPs on stem cell differentiation and proliferation, as well as the mechanisms behind potential toxicity, will be explored. A better understanding of the limitations related to the application of metallic NPs on stem cell proliferation and differentiation will afford clues for optimal design and preparation of metallic NPs for the modulation of stem cell functions and for clinical application in regenerative medicine.

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