scholarly journals Intestinal Tumorigenesis Initiated by Dedifferentiation and Acquisition of Stem-Cell-like Properties

Cell ◽  
2013 ◽  
Vol 152 (1-2) ◽  
pp. 25-38 ◽  
Author(s):  
Sarah Schwitalla ◽  
Alexander A. Fingerle ◽  
Patrizia Cammareri ◽  
Tim Nebelsiek ◽  
Serkan I. Göktuna ◽  
...  
2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Johanna Grinat ◽  
Julian Heuberger ◽  
Ramon Oliveira Vidal ◽  
Neha Goveas ◽  
Frauke Kosel ◽  
...  

AbstractWnt/β-catenin signaling is crucial for intestinal carcinogenesis and the maintenance of intestinal cancer stem cells. Here we identify the histone methyltransferase Mll1 as a regulator of Wnt-driven intestinal cancer. Mll1 is highly expressed in Lgr5+ stem cells and human colon carcinomas with increased nuclear β-catenin. High levels of MLL1 are associated with poor survival of colon cancer patients. The genetic ablation of Mll1 in mice prevents Wnt/β-catenin-driven adenoma formation from Lgr5+ intestinal stem cells. Ablation of Mll1 decreases the self-renewal of human colon cancer spheres and halts tumor growth of xenografts. Mll1 controls the expression of stem cell genes including the Wnt/β-catenin target gene Lgr5. Upon the loss of Mll1, histone methylation at the stem cell promoters switches from activating H3K4 tri-methylation to repressive H3K27 tri-methylation, indicating that Mll1 sustains stem cell gene expression by antagonizing gene silencing through polycomb repressive complex 2 (PRC2)-mediated H3K27 tri-methylation. Transcriptome profiling of Wnt-mutated intestinal tumor-initiating cells reveals that Mll1 regulates Gata4/6 transcription factors, known to sustain cancer stemness and to control goblet cell differentiation. Our results demonstrate that Mll1 is an essential epigenetic regulator of Wnt/β-catenin-induced intestinal tumorigenesis and cancer stemness.


2008 ◽  
Vol 68 (10) ◽  
pp. 3655-3661 ◽  
Author(s):  
Jurrit Zeilstra ◽  
Sander P.J. Joosten ◽  
Maarten Dokter ◽  
Eugène Verwiel ◽  
Marcel Spaargaren ◽  
...  

2020 ◽  
Author(s):  
Min Ji Han ◽  
Won Ji Lee ◽  
Joonhyuk Choi ◽  
Yean Ju Hong ◽  
Sang Jun Uhm ◽  
...  

Author(s):  
D.E. Philpott ◽  
W. Sapp ◽  
C. Williams ◽  
J. Stevenson ◽  
S. Black ◽  
...  

Spermatogonial stem-cell survival after irradiation injury has been studied in rodents by histological counts of surviving cells. Many studies, including previous work from our laboratory, show that the spermatogonial population demonstrates a heterogeneous response to irradiation. The spermatogonia increase in radio-sensitivity as differentiation proceeds through the sequence As - Apr - A1 - A2 - A3 - A4 - In - B. The stem (As) cell is the most resistant and the B cell is the most sensitive. The purpose of this work is to investigate the response of spermatogonial cell to low doses (less than 10 0 rads) of helium particle irradiation.


Author(s):  
D. E. Philpott ◽  
W. Sapp ◽  
C. Williams ◽  
Joann Stevenson ◽  
S. Black

The response of spermatogonial cells to X-irradiation is well documented. It has been shown that there is a radiation resistent stem cell (As) which, after irradiation, replenishes the seminiferous epithelium. Most investigations in this area have dealt with radiation dosages of 100R or more. This study was undertaken to observe cellular responses at doses less than 100R of X-irradiation utilizing a system in which the tissue can be used for light and electron microscopy.Brown B6D2F1 mice aged 16 weeks were exposed to X-irradiation (225KeV; 15mA; filter 0.35 Cu; 50-60 R/min). Four mice were irradiated at each dose level between 1 and 100 rads. Testes were removed 3 days post-irradiation, fixed, and embedded. Sections were cut at 2 microns for light microscopy. After staining, surviving spermatogonia were identified and counted in tubule cross sections. The surviving fraction of spermatogonia compared to control, S/S0, was plotted against dose to give the curve shown in Fig. 1.


Author(s):  
Eric Hallberg ◽  
Lina Hansén

The antennal rudiments in lepidopterous insects are present as disks during the larval stage. The tubular double-walled antennal disk is present beneath the larval antenna, and its inner layer gives rise to the adult antenna during the pupal stage. The sensilla develop from a cluster of cells that are derived from one stem cell, which gives rise to both sensory and enveloping cells. During the morphogenesis of the sensillum these cells undergo major transformations, including cell death. In the moth Agrotis segetum the pupal stage lasts about 14 days (temperature, 25°C). The antennae, clearly seen from the exterior, were dissected and fixed according to standard procedures (3 % glutaraldehyde in 0.15 M cacaodylate buffer, followed by 1 % osmiumtetroxide in the same buffer). Pupae from day 1 to day 8, of both sexes were studied.


2000 ◽  
Vol 111 (3) ◽  
pp. 890-897 ◽  
Author(s):  
Timm Schroeder ◽  
Claudia Lange ◽  
John Strehl ◽  
Ursula Just

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