TY - JOUR

T1 - Tracing the origin of adult intestinal stem cells

AU - Guiu, Jordi

AU - Hannezo, Edouard

AU - Yui, Shiro

AU - Demharter, Samuel

AU - Ulyanchenko, Svetlana

AU - Maimets, Martti

AU - Jørgensen, Anne

AU - Perlman, Signe

AU - Lundvall, Lene

AU - Mamsen, Linn Salto

AU - Larsen, Agnete

AU - Olesen, Rasmus H

AU - Andersen, Claus Yding

AU - Thuesen, Lea Langhoff

AU - Hare, Kristine Juul

AU - Pers, Tune H

AU - Khodosevich, Konstantin

AU - Simons, Benjamin D

AU - Jensen, Kim B

PY - 2019/6

Y1 - 2019/6

N2 - Adult intestinal stem cells are located at the bottom of crypts of Lieberkühn, where they express markers such as LGR51,2 and fuel the constant replenishment of the intestinal epithelium1. Although fetal LGR5-expressing cells can give rise to adult intestinal stem cells3,4, it remains unclear whether this population in the patterned epithelium represents unique intestinal stem-cell precursors. Here we show, using unbiased quantitative lineage-tracing approaches, biophysical modelling and intestinal transplantation, that all cells of the mouse intestinal epithelium-irrespective of their location and pattern of LGR5 expression in the fetal gut tube-contribute actively to the adult intestinal stem cell pool. Using 3D imaging, we find that during fetal development the villus undergoes gross remodelling and fission. This brings epithelial cells from the non-proliferative villus into the proliferative intervillus region, which enables them to contribute to the adult stem-cell niche. Our results demonstrate that large-scale remodelling of the intestinal wall and cell-fate specification are closely linked. Moreover, these findings provide a direct link between the observed plasticity and cellular reprogramming of differentiating cells in adult tissues following damage5-9, revealing that stem-cell identity is an induced rather than a hardwired property.

AB - Adult intestinal stem cells are located at the bottom of crypts of Lieberkühn, where they express markers such as LGR51,2 and fuel the constant replenishment of the intestinal epithelium1. Although fetal LGR5-expressing cells can give rise to adult intestinal stem cells3,4, it remains unclear whether this population in the patterned epithelium represents unique intestinal stem-cell precursors. Here we show, using unbiased quantitative lineage-tracing approaches, biophysical modelling and intestinal transplantation, that all cells of the mouse intestinal epithelium-irrespective of their location and pattern of LGR5 expression in the fetal gut tube-contribute actively to the adult intestinal stem cell pool. Using 3D imaging, we find that during fetal development the villus undergoes gross remodelling and fission. This brings epithelial cells from the non-proliferative villus into the proliferative intervillus region, which enables them to contribute to the adult stem-cell niche. Our results demonstrate that large-scale remodelling of the intestinal wall and cell-fate specification are closely linked. Moreover, these findings provide a direct link between the observed plasticity and cellular reprogramming of differentiating cells in adult tissues following damage5-9, revealing that stem-cell identity is an induced rather than a hardwired property.

KW - Animals

KW - Cell Differentiation

KW - Cell Lineage

KW - Cellular Reprogramming

KW - Female

KW - Fetus/cytology

KW - Intestinal Mucosa/cytology

KW - Intestines/cytology

KW - Male

KW - Mice

KW - Receptors, G-Protein-Coupled/metabolism

KW - Regeneration

KW - Stem Cell Niche

KW - Stem Cells/cytology

U2 - 10.1038/s41586-019-1212-5

DO - 10.1038/s41586-019-1212-5

M3 - Letter

C2 - 31092921

VL - 570

SP - 107

EP - 111

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7759

ER -