The Experts below are selected from a list of 7539 Experts worldwide ranked by ideXlab platform

Frederic J De Sauvage - One of the best experts on this subject based on the ideXlab platform.

  • a reserve stem cell population in Small Intestine renders lgr5 positive cells dispensable
    Nature, 2011
    Co-Authors: Hua Tian, Ophir D Klein, Brian Biehs, Soren Warming, Kevin G Leong, Linda Rangell, Frederic J De Sauvage
    Abstract:

    The Small Intestine Epithelium renews every 2 to 5 days, making it one of the most regenerative mammalian tissues. Genetic inducible fate mapping studies have identified two principal epithelial stem cell pools in this tissue. One pool consists of columnar Lgr5-expressing cells that cycle rapidly and are present predominantly at the crypt base. The other pool consists of Bmi1-expressing cells that largely reside above the crypt base. However, the relative functions of these two pools and their interrelationship are not understood. Here we specifically ablated Lgr5-expressing cells in mice using a human diphtheria toxin receptor (DTR) gene knocked into the Lgr5 locus. We found that complete loss of the Lgr5-expressing cells did not perturb homeostasis of the Epithelium, indicating that other cell types can compensate for the elimination of this population. After ablation of Lgr5-expressing cells, progeny production by Bmi1-expressing cells increased, indicating that Bmi1-expressing stem cells compensate for the loss of Lgr5-expressing cells. Indeed, lineage tracing showed that Bmi1-expressing cells gave rise to Lgr5-expressing cells, pointing to a hierarchy of stem cells in the intestinal Epithelium. Our results demonstrate that Lgr5-expressing cells are dispensable for normal intestinal homeostasis, and that in the absence of these cells, Bmi1-expressing cells can serve as an alternative stem cell pool. These data provide the first experimental evidence for the interrelationship between these populations. The Bmi1-expressing stem cells may represent both a reserve stem cell pool in case of injury to the Small Intestine Epithelium and a source for replenishment of the Lgr5-expressing cells under non-pathological conditions.

  • a reserve stem cell population in Small Intestine renders lgr5 positive cells dispensable
    Nature, 2011
    Co-Authors: Hua Tian, Ophir D Klein, Brian Biehs, Soren Warming, Kevin G Leong, Linda Rangell, Frederic J De Sauvage
    Abstract:

    Two main epithelial stem-cell pools have been previously identified in the Small Intestine Epithelium, but the relative functions of these two pools and their interrelationship are not well understood. Using genetic lineage tracing and lineage ablation studies in mice, Frederic de Sauvage and colleagues have now found that Lgr5-expressing cells are dispensable for normal intestinal homeostasis — the renewal of the Epithelium every few days. In the absence of these cells, Bmi1-expressing cells act as a reserve stem-cell pool and replenish the active Lgr5-expressing stem cells. The Small Intestine Epithelium renews every 2 to 5 days, making it one of the most regenerative mammalian tissues. Genetic inducible fate mapping studies have identified two principal epithelial stem cell pools in this tissue. One pool consists of columnar Lgr5-expressing cells that cycle rapidly and are present predominantly at the crypt base1. The other pool consists of Bmi1-expressing cells that largely reside above the crypt base2. However, the relative functions of these two pools and their interrelationship are not understood. Here we specifically ablated Lgr5-expressing cells in mice using a human diphtheria toxin receptor (DTR) gene knocked into the Lgr5 locus. We found that complete loss of the Lgr5-expressing cells did not perturb homeostasis of the Epithelium, indicating that other cell types can compensate for the elimination of this population. After ablation of Lgr5-expressing cells, progeny production by Bmi1-expressing cells increased, indicating that Bmi1-expressing stem cells compensate for the loss of Lgr5-expressing cells. Indeed, lineage tracing showed that Bmi1-expressing cells gave rise to Lgr5-expressing cells, pointing to a hierarchy of stem cells in the intestinal Epithelium. Our results demonstrate that Lgr5-expressing cells are dispensable for normal intestinal homeostasis, and that in the absence of these cells, Bmi1-expressing cells can serve as an alternative stem cell pool. These data provide the first experimental evidence for the interrelationship between these populations. The Bmi1-expressing stem cells may represent both a reserve stem cell pool in case of injury to the Small Intestine Epithelium and a source for replenishment of the Lgr5-expressing cells under non-pathological conditions.

Christine E Bear - One of the best experts on this subject based on the ideXlab platform.

Mary Pat Moyer - One of the best experts on this subject based on the ideXlab platform.

  • rotating wall vessel coculture of Small Intestine as a prelude to tissue modeling aspects of simulated microgravity
    Experimental Biology and Medicine, 1993
    Co-Authors: Thomas J Goodwin, William F Schroeder, David A Wolf, Mary Pat Moyer
    Abstract:

    AbstractA new low shear stress, low turbulence microcarrier culture system has been developed at NASA's Johnson Space Center that permits large-scale three-dimensional tissue culture. Tissue culture bioreactors called rotating-wall vessels were used in conjunction with multicellular cocultivation to develop a unique in vitro tissue-modeling system. Normal Small Intestine Epithelium and mesenchymal cells were cocultivated on Cytodex-3 microcarriers and were initiated in two phases. Normal Small Intestine mesenchymal cells were inoculated into the rotating-wall vessel at 2 × 105 cells/ml and allowed to attach and proliferate for 2 to 3 days. Normal Small Intestine Epithelium was then added at an innoculum of 2 × 105 cells/ml and cultivation continued for 30 to 40 days. These cocultures attained cell numbers of 4-6 × 106 cells/ml and differentiated to form tissue-like masses of 0.4-0.5 cm with minimal necrosis. The masses displayed apical brush borders, differentiated epithelial cells, cellular polarity, ext...

  • rotating wall vessel coculture of Small Intestine as a prelude to tissue modeling aspects of simulated microgravity
    Experimental Biology and Medicine, 1993
    Co-Authors: Thomas J Goodwin, William F Schroeder, David A Wolf, Mary Pat Moyer
    Abstract:

    : A new low shear stress, low turbulence microcarrier culture system has been developed at NASA's Johnson Space Center that permits large-scale three-dimensional tissue culture. Tissue culture bioreactors called rotating-wall vessels were used in conjunction with multicellular cocultivation to develop a unique in vitro tissue-modeling system. Normal Small Intestine Epithelium and mesenchymal cells were cocultivated on Cytodex-3 microcarriers and were initiated in two phases. Normal Small Intestine mesenchymal cells were inoculated into the rotating-wall vessel at 2 x 10(5) cells/ml and allowed to attach and proliferate for 2 to 3 days. Normal Small Intestine Epithelium was then added at an innoculum of 2 x 10(5) cells/ml and cultivation continued for 30 to 40 days. These cocultures attained cell numbers of 4-6 x 10(6) cells/ml and differentiated to form tissue-like masses of 0.4-0.5 cm with minimal necrosis. The masses displayed apical brush borders, differentiated epithelial cells, cellular polarity, extracellular matrix, and basal lamina. Verification of mesenchymal and epithelial cell expression was determined by immunocytochemistry and scanning electron microscopy. These data suggest that the rotating-wall vessel affords a new tissue culture model for investigation of growth, regulatory, and differentiation processes within normal tissues.

Hua Tian - One of the best experts on this subject based on the ideXlab platform.

  • a reserve stem cell population in Small Intestine renders lgr5 positive cells dispensable
    Nature, 2011
    Co-Authors: Hua Tian, Ophir D Klein, Brian Biehs, Soren Warming, Kevin G Leong, Linda Rangell, Frederic J De Sauvage
    Abstract:

    The Small Intestine Epithelium renews every 2 to 5 days, making it one of the most regenerative mammalian tissues. Genetic inducible fate mapping studies have identified two principal epithelial stem cell pools in this tissue. One pool consists of columnar Lgr5-expressing cells that cycle rapidly and are present predominantly at the crypt base. The other pool consists of Bmi1-expressing cells that largely reside above the crypt base. However, the relative functions of these two pools and their interrelationship are not understood. Here we specifically ablated Lgr5-expressing cells in mice using a human diphtheria toxin receptor (DTR) gene knocked into the Lgr5 locus. We found that complete loss of the Lgr5-expressing cells did not perturb homeostasis of the Epithelium, indicating that other cell types can compensate for the elimination of this population. After ablation of Lgr5-expressing cells, progeny production by Bmi1-expressing cells increased, indicating that Bmi1-expressing stem cells compensate for the loss of Lgr5-expressing cells. Indeed, lineage tracing showed that Bmi1-expressing cells gave rise to Lgr5-expressing cells, pointing to a hierarchy of stem cells in the intestinal Epithelium. Our results demonstrate that Lgr5-expressing cells are dispensable for normal intestinal homeostasis, and that in the absence of these cells, Bmi1-expressing cells can serve as an alternative stem cell pool. These data provide the first experimental evidence for the interrelationship between these populations. The Bmi1-expressing stem cells may represent both a reserve stem cell pool in case of injury to the Small Intestine Epithelium and a source for replenishment of the Lgr5-expressing cells under non-pathological conditions.

  • a reserve stem cell population in Small Intestine renders lgr5 positive cells dispensable
    Nature, 2011
    Co-Authors: Hua Tian, Ophir D Klein, Brian Biehs, Soren Warming, Kevin G Leong, Linda Rangell, Frederic J De Sauvage
    Abstract:

    Two main epithelial stem-cell pools have been previously identified in the Small Intestine Epithelium, but the relative functions of these two pools and their interrelationship are not well understood. Using genetic lineage tracing and lineage ablation studies in mice, Frederic de Sauvage and colleagues have now found that Lgr5-expressing cells are dispensable for normal intestinal homeostasis — the renewal of the Epithelium every few days. In the absence of these cells, Bmi1-expressing cells act as a reserve stem-cell pool and replenish the active Lgr5-expressing stem cells. The Small Intestine Epithelium renews every 2 to 5 days, making it one of the most regenerative mammalian tissues. Genetic inducible fate mapping studies have identified two principal epithelial stem cell pools in this tissue. One pool consists of columnar Lgr5-expressing cells that cycle rapidly and are present predominantly at the crypt base1. The other pool consists of Bmi1-expressing cells that largely reside above the crypt base2. However, the relative functions of these two pools and their interrelationship are not understood. Here we specifically ablated Lgr5-expressing cells in mice using a human diphtheria toxin receptor (DTR) gene knocked into the Lgr5 locus. We found that complete loss of the Lgr5-expressing cells did not perturb homeostasis of the Epithelium, indicating that other cell types can compensate for the elimination of this population. After ablation of Lgr5-expressing cells, progeny production by Bmi1-expressing cells increased, indicating that Bmi1-expressing stem cells compensate for the loss of Lgr5-expressing cells. Indeed, lineage tracing showed that Bmi1-expressing cells gave rise to Lgr5-expressing cells, pointing to a hierarchy of stem cells in the intestinal Epithelium. Our results demonstrate that Lgr5-expressing cells are dispensable for normal intestinal homeostasis, and that in the absence of these cells, Bmi1-expressing cells can serve as an alternative stem cell pool. These data provide the first experimental evidence for the interrelationship between these populations. The Bmi1-expressing stem cells may represent both a reserve stem cell pool in case of injury to the Small Intestine Epithelium and a source for replenishment of the Lgr5-expressing cells under non-pathological conditions.

Katalin Gyomorey - One of the best experts on this subject based on the ideXlab platform.