Sca-1 expression identifies stem cells in the proximal region of prostatic ducts with high capacity to reconstitute prostatic tissue

Stem cells are believed to regulate normal prostatic homeostasis and to play a role in the etiology of prostate cancer and benign prostatic hyperplasia. We show here that the proximal region of mouse prostatic ducts is enriched in a subpopulation of epithelial cells that exhibit three important attributes of epithelial stem cells: they are slow cycling, possess a high in vitro proliferative potential, and can reconstitute highly branched glandular ductal structures in collagen gels. We propose a model of prostatic homeostasis in which mouse prostatic epithelial stem cells are concentrated in the proximal region of prostatic ducts while the transit-amplifying cells occupy the distal region of the ducts. This model can account for many biological differences between cells of the proximal and distal regions, and has implications for prostatic disease formation.

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TGF-β maintains dormancy of prostatic stem cells in the proximal region of ducts

The Journal of Cell Biology ◽

10.1083/jcb.200412015 ◽

2005 ◽

Vol 170 (1) ◽

pp. 81-90 ◽

Cited By ~ 89

Author(s):

Sarah N. Salm ◽

Patricia E. Burger ◽

Sandra Coetzee ◽

Ken Goto ◽

David Moscatelli ◽

...

Keyword(s):

Stem Cells ◽

Transforming Growth Factor ◽

Distal Region ◽

Proximal Region ◽

Cell Compartment ◽

Androgen Ablation ◽

Androgen Withdrawal ◽

Prostatic Diseases ◽

Prostatic Ducts

We have previously shown that prostatic stem cells are located in the proximal region of mouse prostatic ducts. Here, we show that this region responds differently to transforming growth factor (TGF)-β than the distal ductal region and that under physiological conditions androgens and TGF-β are crucial overall regulators of prostatic tissue homeostasis. This conclusion is supported by the observations showing that high levels of TGF-β signaling are present in the quiescent proximal region of ducts in an androgen-replete animal and that cells in this region overexpress Bcl-2, which protects them from apoptosis. Moreover, androgen ablation reverses the proximal-distal TGF-β signaling gradient, leading to an increase in TGF-β signaling in the unprotected distal region (low Bcl-2 expression). This reversal of TGF-β–mediated signaling accompanies apoptosis of cells in the distal region and gland involution after androgen withdrawal. A physiological TGF-β signaling gradient (high proximally and low distally) and its functional correlates are restored after androgen replenishment. In addition to highlighting the regulatory role of androgens and TGF-β, these findings may have important implications for the deregulation of the stem cell compartment in the etiology of proliferative prostatic diseases.

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Biological Aspects and Clinical Applications of Mesenchymal Stem Cells: Key Features You Need to be Aware of.

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666200907121530 ◽

2020 ◽

Vol 21 ◽

Author(s):

Mohammad Saeedi ◽

Muhammad Sadeqi Nezhad ◽

Fatemeh Mehranfar ◽

Mahdieh Golpour ◽

Mohammad Ali Esakandari ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cancer Cells ◽

Immune Modulation ◽

Adult Stem Cells ◽

Inflammatory Diseases ◽

High Capacity ◽

Genetically Engineered ◽

Cartilage Cells ◽

Biological Aspects

: Mesenchymal stem cells (MSCs), a form of adult stem cells, are known to have a self-renewing property and the potential to specialize into a multitude of cells and tissues such as adipocytes, cartilage cells, and fibroblasts. MSCs can migrate and home to the desired target zone where inflammation is present. The unique characteristics of MSCs in repairing, differentiation, regeneration, and its high capacity of immune modulation has attracted tremendous attention for exerting them in clinical purposes, as they contribute to tissue regeneration process and anti-tumor activity. The MSCs-based treatment has demonstrated remarkable applicability towards various diseases such as heart and bone malignancies, and cancer cells. Importantly, genetically engineered MSCs, as a state-of-the-art therapeutic approach, could address some clinical hurdles by systemic secretion of cytokines and other agents with a short half-life and high toxicity. Therefore, understanding the biological aspects and the characteristics of MSCs is an imperative issue of concern. Herein, we provide an overview of the therapeutic application and the biological features of MSCs against different inflammatory diseases and cancer cells. We further shed light on MSCs physiological interaction, such as migration, homing, and tissue repairing mechanisms with different healthy and inflamed tissues.

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High-capacity assay to quantify the clonal heterogeneity in potency of mesenchymal stem cells

BMC Proceedings ◽

10.1186/1753-6561-5-s8-o14 ◽

2011 ◽

Vol 5 (S8) ◽

Cited By ~ 1

Author(s):

Kim C O’Connor ◽

Katie C Russell ◽

Donald G Phinney ◽

Michelle R Lacey ◽

Bonnie L Barrilleaux ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

High Capacity ◽

Clonal Heterogeneity

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In Vitro High-Capacity Assay to Quantify the Clonal Heterogeneity in Trilineage Potential of Mesenchymal Stem Cells Reveals a Complex Hierarchy of Lineage Commitment

Stem Cells ◽

10.1002/stem.312 ◽

2010 ◽

Vol 28 (4) ◽

pp. 788-798 ◽

Cited By ~ 274

Author(s):

Katie C. Russell ◽

Donald G. Phinney ◽

Michelle R. Lacey ◽

Bonnie L. Barrilleaux ◽

Kristin E. Meyertholen ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

High Capacity ◽

Lineage Commitment ◽

Clonal Heterogeneity

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Epigenetic analyses of planarian stem cells demonstrate conservation of bivalent histone modifications in animal stem cells

10.1101/122135 ◽

2017 ◽

Cited By ~ 4

Author(s):

Anish Dattani ◽

Damian Kao ◽

Yuliana Mihaylova ◽

Prasad Abnave ◽

Samantha Hughes ◽

...

Keyword(s):

Stem Cells ◽

Rna Polymerase Ii ◽

Histone Modifications ◽

Cell Function ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Proximal Region ◽

Body Parts ◽

Promoter Regions ◽

Genome Wide

AbstractPlanarian flatworms have an indefinite capacity to regenerate missing or damaged body parts owing to a population of pluripotent adult stems cells called neoblasts (NBs). Currently, little is known about the importance of the epigenetic status of NBs and how histone modifications regulate homeostasis and cellular differentiation. We have developed an improved and optimized ChIP-seq protocol for NBs in Schmidtea mediterranea and have generated genome-wide profiles for the active marks H3K4me3 and H3K36me3, and suppressive marks H3K4me1 and H3K27me3. The genome-wide profiles of these marks were found to correlate well with NB gene expression profiles. We found that genes with little transcriptional activity in the NB compartment but which switch on in post-mitotic progeny during differentiation are bivalent, being marked by both H3K4me3 and H3K27me3 at promoter regions. In further support of this hypothesis bivalent genes also have a high level of paused RNA Polymerase II at the promoter-proximal region. Overall, this study confirms that epigenetic control is important for the maintenance of a NB transcriptional program and makes a case for bivalent promoters as a conserved feature of animal stem cells and not a vertebrate specific innovation. By establishing a robust ChIP-seq protocol and analysis methodology, we further promote planarians as a promising model system to investigate histone modification mediated regulation of stem cell function and differentiation.

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Cancer stem cells in hepatocellular carcinoma: an overview and promising therapeutic strategies

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835918816287 ◽

2018 ◽

Vol 10 ◽

pp. 175883591881628 ◽

Cited By ~ 29

Author(s):

Nuozhou Wang ◽

Shanshan Wang ◽

Ming-Yue Li ◽

Bao-guang Hu ◽

Li-ping Liu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Stem Cells ◽

Cancer Stem Cells ◽

High Capacity ◽

Therapeutic Strategies ◽

Small Subset ◽

Surface Markers ◽

Therapeutic Opportunity ◽

Novel Therapeutic Strategies ◽

Hcc Cells

The poor clinical outcome of hepatocellular carcinoma (HCC) patients is ascribed to the resistance of HCC cells to traditional treatments and tumor recurrence after curative therapies. Cancer stem cells (CSCs) have been identified as a small subset of cancer cells which have high capacity for self-renewal, differentiation and tumorigenesis. Recent advances in the field of liver CSCs (LCSCs) have enabled the identification of CSC surface markers and the isolation of CSC subpopulations from HCC cells. Given their central role in cancer initiation, metastasis, recurrence and therapeutic resistance, LCSCs constitute a therapeutic opportunity to achieve cure and prevent relapse of HCC. Thus, it is necessary to develop therapeutic strategies to selectively and efficiently target LCSCs. Small molecular inhibitors targeting the core stemness signaling pathways have been actively pursued and evaluated in preclinical and clinical studies. Other alternative therapeutic strategies include targeting LCSC surface markers, interrupting the CSC microenvironment, and altering the epigenetic state. In this review, we summarize the properties of CSCs in HCC and discuss novel therapeutic strategies that can be used to target LCSCs.

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Mesenchymal Stem Cells as a Bio Organ for Treatment of Female Infertility

10.20944/preprints202009.0421.v1 ◽

2020 ◽

Author(s):

Sahar Esfandyari ◽

Rishi Man Chugh ◽

Hang-Soo Park ◽

Elie Hobeika ◽

Mara Ulin ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Medical Condition ◽

Polycystic Ovary ◽

High Capacity ◽

Female Infertility ◽

Great Promise ◽

Cell Based Therapy ◽

Therapeutic Outcomes ◽

Cell Sources

Female infertility is a global medical condition that can be caused by various disorders of the reproductive system, including premature ovarian failure (POF), polycystic ovary syndrome (PCOS), endometriosis, Asherman syndrome, and preeclampsia. It affects the quality of life of both patients and couples. Mesenchymal stem cells (MSCs) have received increasing attention as a potential cell-based therapy with several advantages over other cell sources, including greater abundance, fewer ethical considerations, and high capacity for self-renewal and differentiation. Clinical researchers have examined the therapeutic use of MSCs in female infertility. In this review, we discuss recent studies on the use of MSCs in various reproductive disorders that lead to infertility. We also describe the role of microRNAs (miRNAs) and exosomal miRNAs in controlling MSC gene expression and driving MSC therapeutic outcomes. The clinical application of MSCs holds great promise for the treatment of infertility or ovarian insufficiency and to improve reproductive health for a significant number of women worldwide.

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Neural differentiation on aligned fullerene C60 nanowhiskers

Chemical Communications ◽

10.1039/c7cc06395d ◽

2017 ◽

Vol 53 (80) ◽

pp. 11024-11027 ◽

Cited By ~ 21

Author(s):

Fu-Yu Hsieh ◽

Lok Kumar Shrestha ◽

Katsuhiko Ariga ◽

Shan-hui Hsu

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Neural Differentiation ◽

High Capacity ◽

Fullerene C60 ◽

Precipitation Method ◽

Mature Neurons

Highly-aligned fullerene nanowhiskers (C60 NWs) are prepared by a modified liquid–liquid interfacial precipitation method. Neural stem cells on the aligned C60 NWs are oriented and have a high capacity to differentiate into mature neurons.

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