Transplantation of Expanded Fetal Intestinal Progenitors Contributes to Colon Regeneration after Injury
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Transplantation of Expanded Fetal Intestinal Progenitors Contributes to Colon Regeneration after Injury. / Fordham, Robert P; Yui, Shiro; Hannan, Nicholas R F; Soendergaard, Christoffer; Madgwick, Alison; Schweiger, Pawel J; Nielsen, Ole H; Vallier, Ludovic; Pedersen, Roger A; Nakamura, Tetsuya; Watanabe, Mamoru; Jensen, Kim B.
In: Cell Stem Cell, Vol. 13, No. 6, 05.12.2013, p. 734-744.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Transplantation of Expanded Fetal Intestinal Progenitors Contributes to Colon Regeneration after Injury
AU - Fordham, Robert P
AU - Yui, Shiro
AU - Hannan, Nicholas R F
AU - Soendergaard, Christoffer
AU - Madgwick, Alison
AU - Schweiger, Pawel J
AU - Nielsen, Ole H
AU - Vallier, Ludovic
AU - Pedersen, Roger A
AU - Nakamura, Tetsuya
AU - Watanabe, Mamoru
AU - Jensen, Kim B
N1 - Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2013/12/5
Y1 - 2013/12/5
N2 - Regeneration and homeostasis in the adult intestinal epithelium is driven by proliferative resident stem cells, whose functional properties during organismal development are largely unknown. Here, we show that human and mouse fetal intestine contains proliferative, immature progenitors, which can be expanded in vitro as Fetal Enterospheres (FEnS). A highly similar progenitor population can be established during intestinal differentiation of human induced pluripotent stem cells. Established cultures of mouse fetal intestinal progenitors express lower levels of Lgr5 than mature progenitors and propagate in the presence of the Wnt antagonist Dkk1, and new cultures can be induced to form mature intestinal organoids by exposure to Wnt3a. Following transplantation in a colonic injury model, FEnS contribute to regeneration of colonic epithelium by forming epithelial crypt-like structures expressing region-specific differentiation markers. This work provides insight into mechanisms underlying development of the mammalian intestine and points to future opportunities for patient-specific regeneration of the digestive tract.
AB - Regeneration and homeostasis in the adult intestinal epithelium is driven by proliferative resident stem cells, whose functional properties during organismal development are largely unknown. Here, we show that human and mouse fetal intestine contains proliferative, immature progenitors, which can be expanded in vitro as Fetal Enterospheres (FEnS). A highly similar progenitor population can be established during intestinal differentiation of human induced pluripotent stem cells. Established cultures of mouse fetal intestinal progenitors express lower levels of Lgr5 than mature progenitors and propagate in the presence of the Wnt antagonist Dkk1, and new cultures can be induced to form mature intestinal organoids by exposure to Wnt3a. Following transplantation in a colonic injury model, FEnS contribute to regeneration of colonic epithelium by forming epithelial crypt-like structures expressing region-specific differentiation markers. This work provides insight into mechanisms underlying development of the mammalian intestine and points to future opportunities for patient-specific regeneration of the digestive tract.
U2 - 10.1016/j.stem.2013.09.015
DO - 10.1016/j.stem.2013.09.015
M3 - Journal article
C2 - 24139758
VL - 13
SP - 734
EP - 744
JO - Cell Stem Cell
JF - Cell Stem Cell
SN - 1934-5909
IS - 6
ER -
ID: 94413563