scholarly journals MicroRNA Expression Profiling of Normal and Malignant Human Colonic Stem Cells Identifies miRNA92a as a Regulator of the LRIG1 Stem Cell Gene

2020 ◽  
Vol 21 (8) ◽  
pp. 2804 ◽  
Author(s):  
Vignesh Viswanathan ◽  
Lynn Opdenaker ◽  
Shirin Modarai ◽  
Jeremy Z. Fields ◽  
Gregory Gonye ◽  
...  
Keyword(s):  
Stem Cells ◽  
Critical Role ◽  
Human Colon ◽  
Microrna Expression ◽  
Mirna Signature ◽  
Aberrant Expression ◽  
Colon Tumorigenesis ◽  
Colonic Stem Cells ◽  
Cell Gene ◽  
Stem Cell Gene

MicroRNAs (miRNAs) have a critical role in regulating stem cells (SCs) during development, and because aberrant expression of miRNAs occurs in various cancers, our goal was to determine if dysregulation of miRNAs is involved in the SC origin of colorectal cancer (CRC). We previously reported that aldehyde dehydrogenase (ALDH) is a marker for normal and malignant human colonic SCs and tracks SC overpopulation during colon tumorigenesis. MicroRNA expression was studied in ALDH-positive SCs from normal and malignant human colon tissues by Nanostring miRNA profiling. Our findings show that: (1) A unique miRNA signature distinguishes ALDH-positive CRC cells from ALDH-positive normal colonic epithelial cells, (2) Expression of four miRNAs (miRNA200c, miRNA92a, miRNA20a, miRNA93) are significantly altered in CRC SCs compared to normal colonic SCs, (3) miRNA92a expression is also upregulated in ALDH-positive HT29 CRC SCs as compared to ALDH-negative SCs, (4) miRNA92a targets the 3′UTR of LRIG1 SC gene, and (5) miRNA92a modulates proliferation of HT29 CRC cells. Thus, our findings indicate that overexpression of miRNA92a contributes to the SC origin of CRC. Strategies designed to modulate miRNA expression, such as miRNA92a, may provide ways to target malignant SCs and to develop more effective therapies against CRC.

scholarly journals Prrx1 promotes stemness and angiogenesis via activating TGF-β/smad pathway and upregulating proangiogenic factors in glioma

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Zetao Chen ◽  
Yihong Chen ◽  
Yan Li ◽  
Weidong Lian ◽  
Kehong Zheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Therapeutic Strategy ◽  
Critical Role ◽  
Glioma Stem Cells ◽  
Promoter Regions ◽  
Aberrant Expression ◽  
Smad Pathway ◽  
Tgf Β1

AbstractGlioma is one of the most lethal cancers with highly vascularized networks and growing evidences have identified glioma stem cells (GSCs) to account for excessive angiogenesis in glioma. Aberrant expression of paired-related homeobox1 (Prrx1) has been functionally associated with cancer stem cells including GSCs. In this study, Prrx1 was found to be markedly upregulated in glioma specimens and elevated Prrx1 expression was inversely correlated with prognosis of glioma patients. Prrx1 potentiated stemness acquisition in non-stem tumor cells (NSTCs) and stemness maintenance in GSCs, accompanied with increased expression of stemness markers such as SOX2. Prrx1 also promoted glioma angiogenesis by upregulating proangiogenic factors such as VEGF. Consistently, silencing Prrx1 markedly inhibited glioma proliferation, stemness, and angiogenesis in vivo. Using a combination of subcellular proteomics and in vitro analyses, we revealed that Prrx1 directly bound to the promoter regions of TGF-β1 gene, upregulated TGF-β1 expression, and ultimately activated the TGF-β/smad pathway. Silencing TGF-β1 mitigated the malignant behaviors induced by Prrx1. Activation of this pathway cooperates with Prrx1 to upregulate the expression of stemness-related genes and proangiogenic factors. In summary, our findings revealed that Prrx1/TGF-β/smad signal axis exerted a critical role in glioma stemness and angiogeneis. Disrupting the function of this signal axis might represent a new therapeutic strategy in glioma patients.

Feature

2010 ◽  
Vol 14 (03) ◽  
pp. 17-33
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Artificial Cells ◽  
Induced Pluripotent ◽  
Cell Gene ◽  
Stem Cell Gene ◽  
Stem Cell Gene Therapy

Artificial Cells Containing Stem Cells for Liver Failure. Stem Cells and Regenerative Medicine. Towards a Universal Platform for Autologous Stem Cell Gene Therapy: the Induced Pluripotent Stem Cell Breakthrough.

Kallikrein-related peptidase 7 (KLK7) is a proliferative factor that is aberrantly expressed in human colon cancer

2014 ◽  
Vol 395 (9) ◽  
pp. 1075-1086 ◽  
Author(s):  
Francine Walker ◽  
Pascal Nicole ◽  
Abdelhak Jallane ◽  
Antoninus Soosaipillai ◽  
Valentine Mosbach ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Control Cell ◽  
Human Colon ◽  
Tissue Kallikrein ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Aberrant Expression ◽  
Colon Tumorigenesis

Abstract Emerging evidence indicates that serine proteases of the tissue kallikrein-related peptidases family (KLK) are implicated in tumorigenesis. We recently reported the ectopic expression of KLK4 and KLK14 in colonic cancers and their signaling to control cell proliferation. Human tissue kallikrein-related peptidase 7 (KLK7) is often dysregulated in many cancers; however, its role in colon tumorigenesis has not yet been established. In the present study, we analyzed expression of KLK7 in 15 colon cancer cell lines and in 38 human colonic tumors. In many human colon cancer cells, KLK7 mRNA was observed, which leads to KLK7 protein expression and secretion. Furthermore, KLK7 was detected in human colon adenocarcinomas, but it was absent in normal epithelia. KLK7 overexpression in HT29 colon cancer cells upon stable transfection with a KLK7 expression plasmid resulted in increased cell proliferation. Moreover, subcutaneous inoculation of transfected cells into nude mice led to increased tumor growth that was associated with increased tumor cell proliferation as reflected by a positive Ki-67 staining. Our results demonstrate the aberrant expression of KLK7 in colon cancer cells and tissues and its involvement in cell proliferation in vitro and in vivo. Thus, KLK7 may represent a potential therapeutic target for human colon tumorigenesis.

scholarly journals Aldehyde Dehydrogenase 1 Is a Marker for Normal and Malignant Human Colonic Stem Cells (SC) and Tracks SC Overpopulation during Colon Tumorigenesis

2009 ◽  
Vol 69 (8) ◽  
pp. 3382-3389 ◽  
Author(s):  
Emina H. Huang ◽  
Mark J. Hynes ◽  
Tao Zhang ◽  
Christophe Ginestier ◽  
Gabriela Dontu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Aldehyde Dehydrogenase ◽  
Aldehyde Dehydrogenase 1 ◽  
Colon Tumorigenesis ◽  
Colonic Stem Cells

scholarly journals Regenerative neurogenic response from glia requires insulin driven neuron-glia communication

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Neale J Harrison ◽  
Elizabeth Connolly ◽  
Alicia Gascón Gubieda ◽  
Zidan Yang ◽  
Benjamin Altenhein ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
De Novo ◽  
Lineage Tracing ◽  
Cell Gene Expression ◽  
The Central Nervous System ◽  
Induced Neural Stem Cell ◽  
Islet Antigen ◽  
Cell Gene ◽  
Stem Cell Gene

Understanding how injury to the Central Nervous System (CNS) induces de novo neurogenesis in animals would help promote regeneration in humans. Regenerative neurogenesis could originate from glia and glial Neuron-Glia antigen-2 (NG2) may sense injury-induced neuronal signals, but these are unknown. Here, we used Drosophila to search for genes functionally related the NG2 homologue kon-tiki (kon), and identified Islet Antigen-2 (Ia-2), required in neurons for insulin secretion. Alterations in Ia-2 function induced neural stem cell gene expression, injury increased ia-2 expression and induced ectopic neural stem cells. Using genetic analysis and lineage tracing, we demonstrate that Ia-2 and Kon regulate Drosophila insulin-like peptide 6 (Dilp-6), to induce glial proliferation and neural stem cells from glia. Ectopic neural stem cells can divide, and limited de novo neurogenesis could be traced back to glial cells. Altogether, Ia-2 and Dilp-6 drive a neuron-glia relay that restores glia, and reprograms glia into neural stem cells for regeneration.

scholarly journals Long noncoding RNA Meg3 sponges miR-708 to inhibit intestinal tumorigenesis via SOCS3-repressed cancer stem cells growth

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Shuo Zhang ◽  
Wei-Wei Ji ◽  
Wei Wei ◽  
Li-Xing Zhan ◽  
Xuan Huang
Keyword(s):  
Stem Cells ◽  
Noncoding Rna ◽  
Early Stage ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Clinical Samples ◽  
Loss Of Function ◽  
Signaling Axis ◽  
Colonic Stem Cells

Abstract Background Colorectal cancer (CRC) remains the most common gastrointestinal cancer and a leading cause of cancer deaths worldwide, with most showing pathologies indicating the malignant transformation of early stage intestinal stem cells. The long non-coding RNA Meg3, which functions as a tumor suppressor, has been reported to be abnormal in multiple tumorigenesis events; however, the underlying mechanism by which Meg3 contributes to the malignant proliferation of colonic stem cells remains unclear. Methods We analyzed the expression levels of Meg3, miR-708, and SOCS3 in samples from Apc loss-of-function (Apcmin) mice and patients with CRC, particularly in colonic crypt cells. Apcmin mice and AMO/DSS-induced mice model (in vivo) and organoid culture system (in vitro) were used to explore the effect of the Meg3/miR-708/SOCS3 axis on tumorigenesis in the colon. In vitro, we performed RNApull-down, RNA immunoprecipitation, and luciferase reporter assays using DLD1 and RKO cell lines. Findings The Meg3/miR-708/SOCS3 signaling axis plays a critical role in the early stage of CRC development. Our data showed Meg3 levels negatively correlate with miR-708 levels both in clinical samples and in the Apcmin mouse model, which indicated that Meg3 acts as a competitive endogenous RNA (ceRNA) of miR-708. Then, miR-708 served as an oncogene, inducing neoplasia in both Apcmin mice and cultured colonic organoids. Put together, miR-708 appears to promote malignant proliferation of colonic stem cells by targeting SOCS3/STAT3 signaling. Interpretation These data revealed that Meg3 sponges miR-708 to inhibit CRC development via SOCS3-mediated repression of the malignant proliferation of colonic stem cells. The Meg3/miR-708/SOCS3 signaling axis provides potential targets for the diagnosis and treatment of CRC, particularly early stage CRC.

scholarly journals A mutant p53-dependent embryonic stem cell gene signature is associated with augmented tumorigenesis of stem cells

2018 ◽  
pp. canres.0805.2018 ◽  
Author(s):  
Gabriela Koifman ◽  
Yoav shetzer ◽  
Shay Eizenberger ◽  
Hilla Solomon ◽  
Ron Rotkopf ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Gene Signature ◽  
Mutant P53 ◽  
Cell Gene ◽  
Stem Cell Gene

scholarly journals DNMT3A-dependent DNA methylation is required for spermatogonial stem cells to commit to spermatogenesis

2021 ◽  
Author(s):  
Mathilde Dura ◽  
Aurelie Teissandier ◽  
Melanie Armand ◽  
Joan Barau ◽  
Lorraine Bonneville ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cell ◽  
Dna Methyltransferase ◽  
Developmental Trajectories ◽  
Critical Role ◽  
Spermatogonial Stem Cell ◽  
Rna Seq ◽  
Epigenetic Programming ◽  
Cell Gene ◽  
Stem Cell Gene

DNA methylation plays a critical role in spermatogenesis, as evidenced by the male sterility of DNA methyltransferase (DNMT) mutant mice. Here, we report a striking division of labor in the establishment of the methylation landscape of male germ cells and its functions in spermatogenesis: while DNMT3C is essential for preventing retrotransposons from interfering with meiosis, DNMT3A broadly methylates the genome - at the exception of DNMT3C-dependent retrotransposons - and controls spermatogonial stem cell (SSC) plasticity. By reconstructing developmental trajectories through single-cell RNA-seq and by profiling chromatin states, we found that Dnmt3A mutant SSCs can only self-renew and no longer differentiate due to spurious enhancer activation that enforces an irreversible stem cell gene program. We therefore provide a novel function for DNA methylation in male fertility: the epigenetic programming of SSC commitment to differentiation and to life-long spermatogenesis supply.

CHARACTERIZATION OF ENDOGENOUS STEM CELLS FROM THE MOUSE PENIS THAT EXPRESS AN EMBRYONIC STEM CELL GENE AND UNDERGO DIFFERENTIATION INTO SEVERAL CELL LINEAGES

2009 ◽  
Vol 181 (4S) ◽  
pp. 43-43 ◽  
Author(s):  
Dolores Vernet ◽  
Sanaz Heydarkhan ◽  
Istvan Kovanecz ◽  
Yan-H Lue ◽  
Jacob Rajfer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Cell Lineages ◽  
Cell Gene ◽  
Stem Cell Gene
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