scholarly journals An NRF2 Perspective on Stem Cells and Ageing

2021 ◽  
Vol 2 ◽  
Author(s):  
Matthew Dodson ◽  
Annadurai Anandhan ◽  
Donna D. Zhang ◽  
Lalitha Madhavan
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Brain Plasticity ◽  
Adult Brain ◽  
Cellular Redox ◽  
Age Related ◽  
Regenerative Activity ◽  
And Function ◽  
Stem Cell State

Redox and metabolic mechanisms lie at the heart of stem cell survival and regenerative activity. NRF2 is a major transcriptional controller of cellular redox and metabolic homeostasis, which has also been implicated in ageing and lifespan regulation. However, NRF2’s role in stem cells and their functioning with age is only just emerging. Here, focusing mainly on neural stem cells, which are core to adult brain plasticity and function, we review recent findings that identify NRF2 as a fundamental player in stem cell biology and ageing. We also discuss NRF2-based molecular programs that may govern stem cell state and function with age, and implications of this for age-related pathologies.

scholarly journals The hematopoietic landscape at single-cell resolution reveals unexpected stem cell features in naked mole-rats

2019 ◽  
Author(s):  
Stephan Emmrich ◽  
Marco Mariotti ◽  
Masaki Takasugi ◽  
Maggie E. Straight ◽  
Alexandre Trapp ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Stem Cell ◽  
Single Cell ◽  
Cell Biology ◽  
List Type ◽  
Hematopoietic Stem ◽  
Age Related ◽  
Mole Rat ◽  
Naked Mole Rat

SUMMARYNaked mole-rats are the longest-lived rodents endowed with resistance to cancer and age-related diseases, yet their stem cell characteristics remain enigmatic. We profiled the naked mole-rat hematopoietic system down to single-cell resolution, and identified several unique features likely contributing to longevity. In adult naked mole-rats red blood cells are formed in spleen and marrow, a neotenic feature beneficial for hypoxic environments and to prevent anemia. Platelet numbers are lower compared to short-lived mice, which may preclude age-related platelet increase and thrombosis. T cells mature in thymus and lymph nodes, providing a supply of T cells after age-related thymus involution. The pool of quiescent stem cells is higher than in mice, and HSCs overexpress an oxidative phosphorylation signature, revealing a new paradigm of stem cell metabolism to benefit longevity and oppose oncogenesis. Our work provides a platform to study immunology and stem cell biology in an animal model of healthy aging.HIGHLIGHTSFlow cytometry labelling panel to purify viable naked mole-rat HSPCsThe spleen as the major site of erythropoiesis in the naked mole-ratNaked mole-rats show extrathymic T-cell development under homeostatic conditionsNaked mole-rat hematopoietic stem cells (HSCs) have high OXPHOS activity

scholarly journals Optimized Stem Cell Detection Using the DyeCycle-Triggered Side Population Phenotype

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Maximilian Boesch ◽  
Dominik Wolf ◽  
Sieghart Sopper
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cell Biology ◽  
Side Population ◽  
Blue Laser ◽  
Cell Detection ◽  
Target Populations ◽  
And Function ◽  
Transporter Expression

Tissue and cancer stem cells are highly attractive target populations for regenerative medicine and novel potentially curative anticancer therapeutics. In order to get a better understanding of stem cell biology and function, it is essential to reproducibly identify these stem cells from biological samples for subsequent characterization or isolation. ABC drug transporter expression is a hallmark of stem cells. This is utilized to identify (cancer) stem cells by exploiting their dye extrusion properties, which is referred to as the “side population assay.” Initially described for high-end flow cytometers equipped with ultraviolet lasers, this technique is now also amenable for a broader scientific community, owing to the increasing availability of violet laser-furnished cytometers and the advent of DyeCycle Violet (DCV). Here, we describe important technical aspects of the DCV-basedside population assayand discuss potential pitfalls and caveats helping scientists to establish a valid and reproducible DCV-basedside population assay. In addition, we investigate the suitability of blue laser-excitable DyeCycle dyes for side population detection. This knowledge will help to improve and standardize detection and isolation of stem cells based on their expression of ABC drug transporters.

scholarly journals Potential Use of Stem Cells for Kidney Regeneration

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Takashi Yokoo ◽  
Kei Matsumoto ◽  
Shinya Yokote
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Research ◽  
Cell Biology ◽  
Current Knowledge ◽  
Kidney Regeneration ◽  
Major Step ◽  
Kidney Dialysis ◽  
Organ Regeneration ◽  
Renal Stem Cell

Significant advances have been made in stem cell research over the past decade. A number of nonhematopoietic sources of stem cells (or progenitor cells) have been identified, including endothelial stem cells and neural stem cells. These discoveries have been a major step toward the use of stem cells for potential clinical applications of organ regeneration. Accordingly, kidney regeneration is currently gaining considerable attention to replace kidney dialysis as the ultimate therapeutic strategy for renal failure. However, due to anatomic complications, the kidney is believed to be the hardest organ to regenerate; it is virtually impossible to imagine such a complicated organ being completely rebuilt from pluripotent stem cells by gene or chemical manipulation. Nevertheless, several groups are taking on this big challenge. In this manuscript, current advances in renal stem cell research are reviewed and their usefulness for kidney regeneration discussed. We also reviewed the current knowledge of the emerging field of renal stem cell biology.

Distribution of amniotic stem cells in human term amnion membrane

Microscopy ◽  
2021 ◽  
Author(s):  
Nobuyuki Koike ◽  
Jun Sugimoto ◽  
Motonori Okabe ◽  
Kenichi Arai ◽  
Makiko Nogami ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Markers ◽  
Epithelial Stem Cells ◽  
Human Amnion ◽  
Transporter Protein ◽  
Amniotic Mesenchymal Stem Cells ◽  
Amnion Membrane ◽  
And Function ◽  
A Site

Abstract Amnion membrane studies related to miscarriage have been conducted in the field of obstetrics and gynecology. However, the distribution of stem cells within the amnion and the differences in the properties of each type of stem cells are still not well understood. We address this gap in knowledge in the present study where we morphologically classified the amnion membrane, and we clarified the distribution of stem cells here to identify functionally different amniotic membrane–derived stem cells. The amnion can be divided into a site that is continuous with the umbilical cord (region A), a site that adheres to the placenta (region B), and a site that is located opposite the placenta (region C). We found that human amnion epithelial stem cells (HAECs) that strongly express stem cell markers were abundant in area A. HAEC not only expressesed stem cell-specific surface markers TRA-1-60, Tra-1-81, SSEA4, SSEA3, but was also OCT-3/4 positive and had alkaline phosphatase activity. Human amniotic mesenchymal stem cells expressed KLF-A, OCTA, Oct3/4, c-MYC and Sox2 which is transcription factor. Especially, in regions A and B they have expressed CD73, and the higher expression of BCRP which is drug excretion transporter protein than the other parts. These data suggest that different types of stem cells may have existed in different area. The understanding the relation with characteristics of the stem cells in each area and function would allow for the efficient harvest of suitable HAE and HAM stem cells as using tool for regenerative medicine.

scholarly journals Lineage specification of early embryos and embryonic stem cells at the dawn of enabling technologies

2017 ◽  
Vol 4 (4) ◽  
pp. 533-542 ◽  
Author(s):  
Guangdun Peng ◽  
Patrick P. L. Tam ◽  
Naihe Jing
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Developmental Process ◽  
Embryonic Stem ◽  
Molecular Signaling ◽  
Lineage Specification ◽  
Genomic Technologies ◽  
Enabling Technologies ◽  
Stem Cell Pluripotency

Abstract Establishment of progenitor cell populations and lineage diversity during embryogenesis and the differentiation of pluripotent stem cells is a fascinating and intricate biological process. Conceptually, an understanding of this developmental process provides a framework to integrate stem-cell pluripotency, cell competence and differentiating potential with the activity of extrinsic and intrinsic molecular determinants. The recent advent of enabling technologies of high-resolution transcriptome analysis at the cellular, population and spatial levels proffers the capability of gaining deeper insights into the attributes of the gene regulatory network and molecular signaling in lineage specification and differentiation. In this review, we provide a snapshot of the emerging enabling genomic technologies that contribute to the study of development and stem-cell biology.

scholarly journals First person – Federico Pecori

2020 ◽  
Vol 133 (20) ◽  
pp. jcs255166
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Cell Biology ◽  
Embryonic Stem ◽  
Early Career ◽  
First Person ◽  
Receptor Endocytosis ◽  
Early Career Researchers ◽  
Selection Of

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Federico Pecori is first author on ‘Mucin-type O-glycosylation controls pluripotency in mouse embryonic stem cells via Wnt receptor endocytosis’, published in JCS. Federico is a PhD student in the lab of Shoko Nishihara at the Laboratory of Cell Biology, Department of Bioinformatics, Soka University, Tokyo, Japan, where he is interested in the mechanisms regulating stem cell identity.

scholarly journals The Winding Road of Cardiac Regeneration—Stem Cell Omics in the Spotlight

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 255 ◽  
Author(s):  
Miruna Mihaela Micheu ◽  
Alina Ioana Scarlatescu ◽  
Alexandru Scafa-Udriste ◽  
Maria Dorobantu
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Unmet Need ◽  
Cardiac Regeneration ◽  
Cell Types ◽  
Great Promise ◽  
Omics Data

Despite significant progress in treating ischemic cardiac disease and succeeding heart failure, there is still an unmet need to develop effective therapeutic strategies given the persistent high-mortality rate. Advances in stem cell biology hold great promise for regenerative medicine, particularly for cardiac regeneration. Various cell types have been used both in preclinical and clinical studies to repair the injured heart, either directly or indirectly. Transplanted cells may act in an autocrine and/or paracrine manner to improve the myocyte survival and migration of remote and/or resident stem cells to the site of injury. Still, the molecular mechanisms regulating cardiac protection and repair are poorly understood. Stem cell fate is directed by multifaceted interactions between genetic, epigenetic, transcriptional, and post-transcriptional mechanisms. Decoding stem cells’ “panomic” data would provide a comprehensive picture of the underlying mechanisms, resulting in patient-tailored therapy. This review offers a critical analysis of omics data in relation to stem cell survival and differentiation. Additionally, the emerging role of stem cell-derived exosomes as “cell-free” therapy is debated. Last but not least, we discuss the challenges to retrieve and analyze the huge amount of publicly available omics data.

scholarly journals Antioxidant Effects of Caffeic Acid Lead to Protection of Drosophila Intestinal Stem Cell Aging

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiao Sheng ◽  
Yuedan Zhu ◽  
Juanyu Zhou ◽  
La Yan ◽  
Gang Du ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Caffeic Acid ◽  
Stress Responses ◽  
Adult Stem Cells ◽  
Cell Function ◽  
Cell Aging ◽  
Positive Effects ◽  
Age Related ◽  
Tissue Aging

The dysfunction or exhaustion of adult stem cells during aging is closely linked to tissue aging and age-related diseases. Circumventing this aging-related exhaustion of adult stem cells could significantly alleviate the functional decline of organs. Therefore, identifying small molecular compounds that could prevent the age-related decline of stem cell function is a primary goal in anti-aging research. Caffeic acid (CA), a phenolic compound synthesized in plants, offers substantial health benefits for multiple age-related diseases and aging. However, the effects of CA on adult stem cells remain largely unknown. Using the Drosophila midgut as a model, this study showed that oral administration with CA significantly delayed age-associated Drosophila gut dysplasia caused by the dysregulation of intestinal stem cells (ISCs) upon aging. Moreover, administering CA retarded the decline of intestinal functions in aged Drosophila and prevented hyperproliferation of age-associated ISC by suppressing oxidative stress-associated JNK signaling. On the other hand, CA supplementation significantly ameliorated the gut hyperplasia defect and reduced environmentally induced mortality, revealing the positive effects of CA on tolerance to stress responses. Taken together, our findings report a crucial role of CA in delaying age-related changes in ISCs of Drosophila.

Establishment of human OCT4 as a putative HSP90 client protein : a case for HSP90 chaperoning pluripotency

2015 ◽  
Author(s):  
◽  
Jason Neville Sterrenberg
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Stem Cell ◽  
Cell Biology ◽  
Therapeutic Potential ◽  
Stem Cell Biology ◽  
Client Protein ◽  
Hsp90 Inhibition ◽  
Regulated Gene Expression ◽  
Hsp90 Client Protein

The therapeutic potential of stem cells is already being harnessed in clinical trails. Of even greater therapeutic potential has been the discovery of mechanisms to reprogram differentiated cells into a pluripotent stem cell-like state known as induced pluripotent stem cells (iPSCs). Stem cell nature is governed and maintained by a hierarchy of transcription factors, the apex of which is OCT4. Although much research has elucidated the transcriptional regulation of OCT4, OCT4 regulated gene expression profiles and OCT4 transcriptional activation mechanisms in both stem cell biology and cellular reprogramming to iPSCs, the fundamental biochemistry surrounding the OCT4 transcription factor remains largely unknown. In order to analyze the biochemical relationship between HSP90 and human OCT4 we developed an exogenous active human OCT4 expression model with human OCT4 under transcriptional control of a constitutive promoter. We identified the direct interaction between HSP90 and human OCT4 despite the fact that the proteins predominantly display differential subcellular localizations. We show that HSP90 inhibition resulted in degradation of human OCT4 via the ubiquitin proteasome degradation pathway. As human OCT4 and HSP90 did not interact in the nucleus, we suggest that HSP90 functions in the cytoplasmic stabilization of human OCT4. Our analysis suggests HSP90 inhibition inhibits the transcriptional activity of human OCT4 dimers without affecting monomeric OCT4 activity. Additionally our data suggests that the HSP90 and human OCT4 complex is modulated by phosphorylation events either promoting or abrogating the interaction between HSP90 and human OCT4. Our data suggest that human OCT4 displays the characteristics describing HSP90 client proteins, therefore we identify human OCT4 as a putative HSP90 client protein. The regulation of the transcription factor OCT4 by HSP90 provides fundamental insights into the complex biochemistry of stem cell biology. This may also be suggestive that HSP90 not only regulates stem cell biology by maintaining routine cellular homeostasis but additionally through the direct regulation of pluripotency factors.

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