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Author: Reina Aoki Publisher: ISBN: Category : Languages : en Pages : 156
Book Description
The intestinal epithelium is one of the most rapidly self-renewing tissues in the body and thus the ideal tissue for studying somatic progenitor and stem cell biology. The intestinal epithelium is composed of a single layer of cells that contains four major differentiated cell types as well as intestinal stem cells (ISCs) and progenitor cells that replenish differentiated cells throughout life. However, the molecular mechanisms that govern the self-renewal and differentiation of ISCs are only partially understood. Previously, one of the terminally differentiated epithelial cell types, the Paneth cells, were proposed to be the ISC "niche." However, subsequent studies have found ablation of Paneth cells in mice showed no effect on either stem cell maintenance or proliferation. I have analyzed the poorly understood mesenchymal contribution to epithelial stem cell maintenance and homeostasis by generating Foxl1-hDTR transgenic mice, in which the human diphtheria toxin receptor (hDTR ) is placed under the control of the Foxl1 promoter. Foxl1 is exclusively expressed in the subepithelial mesenchyme of the adult gastrointestinal tract. Ablation of Foxl1+ mesenchymal cells resulted in severe weight loss and disruption of epithelial architecture and a dramatic reduction in proliferation of both epithelial stem and transit-amplifying progenitor cells. I found that these effects are caused by the loss of activated Wnt/[beta]-catenin signaling signaling in the epithelium. Taken together, I have identified a novel mesenchymal ISC niche that supports both proliferation and maintenance of stem cells possibly through providing important Wnt ligands.
Author: Reina Aoki Publisher: ISBN: Category : Languages : en Pages : 156
Book Description
The intestinal epithelium is one of the most rapidly self-renewing tissues in the body and thus the ideal tissue for studying somatic progenitor and stem cell biology. The intestinal epithelium is composed of a single layer of cells that contains four major differentiated cell types as well as intestinal stem cells (ISCs) and progenitor cells that replenish differentiated cells throughout life. However, the molecular mechanisms that govern the self-renewal and differentiation of ISCs are only partially understood. Previously, one of the terminally differentiated epithelial cell types, the Paneth cells, were proposed to be the ISC "niche." However, subsequent studies have found ablation of Paneth cells in mice showed no effect on either stem cell maintenance or proliferation. I have analyzed the poorly understood mesenchymal contribution to epithelial stem cell maintenance and homeostasis by generating Foxl1-hDTR transgenic mice, in which the human diphtheria toxin receptor (hDTR ) is placed under the control of the Foxl1 promoter. Foxl1 is exclusively expressed in the subepithelial mesenchyme of the adult gastrointestinal tract. Ablation of Foxl1+ mesenchymal cells resulted in severe weight loss and disruption of epithelial architecture and a dramatic reduction in proliferation of both epithelial stem and transit-amplifying progenitor cells. I found that these effects are caused by the loss of activated Wnt/[beta]-catenin signaling signaling in the epithelium. Taken together, I have identified a novel mesenchymal ISC niche that supports both proliferation and maintenance of stem cells possibly through providing important Wnt ligands.
Author: Gary Hime Publisher: Springer Science & Business Media ISBN: 9400766211 Category : Medical Languages : en Pages : 370
Book Description
This volume describes the latest findings on transcriptional and translational regulation of stem cells. Both transcriptional activators and repressors have been shown to be crucial for the maintenance of the stem cell state. A key element of stem cell maintenance is repression of differentiation factors or developmental genes – achieved transcriptionally, epigenetically by the Polycomb complex, and post-transcriptionally by RNA-binding proteins and microRNAs. This volume takes two approaches to this topic – (1) illustrating the general principles outlined above through a series of different stem cell examples – embryonic, iPS and adult stem cells, and (2) describing several molecular families that have been shown to have roles in regulation of multiple stem cell populations.
Author: Antoine Gleizes Publisher: ISBN: Category : Medicine Languages : en Pages :
Book Description
Colorectal cancer (CRC) is one of the most frequent cancers worldwide. Current treatments include surgery and chemotherapy, but disease recurrence occurs frequently. The continuous renewal of intestinal epithelium relies on the presence of intestinal stem cells that are also at the origin of CRC and contribute to therapy resistance and metastatic dissemination. Several nuclear signaling pathways and transcription factors regulate both intestinal cell homeostasis and tumorigenesis. However, the transcriptional events that govern the emergence of aggressive therapy-resistant cancer stem cells are still poorly defined. This review summarizes the relevance of transcription factors in intestinal stem cell biology and their involvement in colon cancer development and drug resistance.
Author: Publisher: Academic Press ISBN: 9780128134818 Category : Science Languages : en Pages : 150
Book Description
Advances in Stem Cells and Their Niches addresses stem cells during development, homeostasis, and disease/injury of the respective organs, presenting new developments in the field, including new data on disease and clinical applications. Video content illustrates such areas as protocols, transplantation techniques, and work with mice. Explores not only reviews of research, but also shares methods, protocols, and transplantation techniques Contains video content to illustrate such areas as protocols, transplantation techniques, and work with mice Each volume concentrates on one organ, making this a unique publication
Author: Melanie Alice Eshelman Publisher: ISBN: Category : Languages : en Pages :
Book Description
The intestinal epithelium absorbs nutrients and forms a barrier between luminal microorganisms and immune cells in the submucosa. Intestinal epithelial cells (IECs) are continuously replenished by intestinal stem cells, which generate both secretory and absorptive lineages of differentiated IECs. The expression of genes involved in IEC proliferation and differentiation must be precisely controlled to ensure epithelial barrier integrity and prevent malignancy. RNA-binding proteins fine-tune gene expression post-transcriptionally and have been implicated in the maintenance of IEC homeostasis. We investigated the role of RNA-binding protein, Tristetraprolin (TTP), encoded by the Zfp36 gene, in IEC homeostasis and disease. TTP binds to AU-rich elements in the 3UTR of a subset of mRNAs and targets them for degradation. Many established TTP target genes encode inflammatory modulators and proto-oncogenes, however it is unknown what genes are regulated by TTP in IECs. To elucidate a functional role for TTP in the intestinal epithelium, we generated IEC mice, which lack expression of Zfp36 in the IECs. We found that epithelial TTP is largely dispensable for intestinal homeostasis. However, the colons of IEC mice exhibit increased crypt depth and a mild expansion of the proliferative zone. Additionally, RNA-sequencing of colon tissue from control (Zfp36fl/fl) and IEC mice identified IEC-specific TTP target genes, including nitric oxide synthase 2 (Nos2), which, we demonstrate, is regulated by TTP through AU-rich elements in its 3UTR. Strikingly, upon DSS-induced colitis, IEC mice were protected from the pathologies associated with colitis, including weight loss, colon shortening, and perturbed colonic mucosal architecture. Additionally, IEC mice had enhanced tumor growth in AOM-DSS induced colitis-associated cancer. These findings uncover roles for TTP in IECs, including modulating Nos2 expression, regulating IEC regeneration, and suppressing tumor expansion.
Author: Torben Heick Jensen Publisher: Springer Science & Business Media ISBN: 1441978410 Category : Medical Languages : en Pages : 161
Book Description
The diversity of RNAs inside living cells is amazing. We have known of the more “classic” RNA species: mRNA, tRNA, rRNA, snRNA and snoRNA for some time now, but in a steady stream new types of molecules are being described as it is becoming clear that most of the genomic information of cells ends up in RNA. To deal with the enormous load of resulting RNA processing and degradation reactions, cells need adequate and efficient molecular machines. The RNA exosome is arising as a major facilitator to this effect. Structural and functional data gathered over the last decade have illustrated the biochemical importance of this multimeric complex and its many co-factors, revealing its enormous regulatory power. By gathering some of the most prominent researchers in the exosome field, it is the aim of this volume to introduce this fascinating protein complex as well as to give a timely and rich account of its many functions. The exosome was discovered more than a decade ago by Phil Mitchell and David Tollervey by its ability to trim the 3’end of yeast, S. cerevisiae, 5. 8S rRNA. In a historic account they laid out the events surrounding this identification and the subsequent birth of the research field. In the chapter by Kurt Januszyk and Christopher Lima the structural organization of eukaryotic exosomes and their evolutionary counterparts in bacteria and archaea are discussed in large part through presentation of structures.
Author: C. Potten Publisher: Elsevier ISBN: 0080541763 Category : Science Languages : en Pages : 497
Book Description
Stem cells are relatively undifferentiated cells which are the permanent lineage ancestor cells of tissues. Newly developed molecular biological techniques and probes have made possible dramatic advances in our ability to study the lineage development of stem cells. A major impetus to develop these techniques has been to identify specific stem cells for gene therapy purposes. The role that stem cells play in the development of cancer is also an important area. This book provides up-to-date reviews on a wide variety of stem cell systems by world experts. Chapters range from descriptions of the current knowledge of the biology of stem cells, to current molecular biological approaches and clinical implications. Oncologists and cell biologists will find this book of particular interest. It will also be usefule to radiobiologist, biotechnologists, and gene therapists. - Provides reviews of stem cell systems by world experts - Covers stem cell biology in plants, invertebrates, and mammals - Presents clinical implications of stem cell differentiation
Author: Reina Aoki
Author: Reina Aoki
Author: Gary Hime
Author: Dane Cheasley
Author: Antoine Gleizes
Author: 
Author: 
Author: Melanie Alice Eshelman
Author: Linxia Zhang
Author: Torben Heick Jensen
Author: C. Potten