Tracing the origin of adult intestinal stem cells

Jordi Guiu; Edouard Hannezo; Shiro Yui; Samuel Demharter; Svetlana Ulyanchenko; Martti Maimets; Anne Jørgensen; Signe Perlman; Lene Lundvall; Linn Salto Mamsen; Agnete Larsen; Rasmus H Olesen; Claus Yding Andersen; Lea Langhoff Thuesen; Kristine Juul Hare; Tune H Pers; Konstantin Khodosevich; Benjamin D Simons; Kim B Jensen

doi:10.1038/s41586-019-1212-5

Tracing the origin of adult intestinal stem cells

Jordi Guiu, Edouard Hannezo, Shiro Yui, Samuel Demharter, Svetlana Ulyanchenko, Martti Maimets, Anne Jørgensen, Signe Perlman, Lene Lundvall, Linn Salto Mamsen, Agnete Larsen, Rasmus H Olesen, Claus Yding Andersen, Lea Langhoff Thuesen, Kristine Juul Hare, Tune H Pers, Konstantin Khodosevich, Benjamin D Simons, Kim B Jensen

38 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Nature
Volume	570
Issue number	7759
Pages (from-to)	107-111
Number of pages	5
ISSN	0028-0836
DOIs	https://doi.org/10.1038/s41586-019-1212-5
Publication status	Published - 6 Jun 2019

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Guiu, J., Hannezo, E., Yui, S., Demharter, S., Ulyanchenko, S., Maimets, M., Jørgensen, A., Perlman, S., Lundvall, L., Mamsen, L. S., Larsen, A., Olesen, R. H., Andersen, C. Y., Thuesen, L. L., Hare, K. J., Pers, T. H., Khodosevich, K., Simons, B. D., & Jensen, K. B. (2019). Tracing the origin of adult intestinal stem cells. Nature, 570(7759), 107-111. https://doi.org/10.1038/s41586-019-1212-5

Guiu, J, Hannezo, E, Yui, S, Demharter, S, Ulyanchenko, S , Maimets, M, Jørgensen, A, Perlman, S, Lundvall, L, Mamsen, LS, Larsen, A, Olesen, RH, Andersen, CY, Thuesen, LL, Hare, KJ , Pers, TH , Khodosevich, K, Simons, BD & Jensen, KB 2019, 'Tracing the origin of adult intestinal stem cells', Nature, vol. 570, no. 7759, pp. 107-111. https://doi.org/10.1038/s41586-019-1212-5

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title = "Tracing the origin of adult intestinal stem cells",

abstract = "Adult intestinal stem cells are located at the bottom of crypts of Lieberk{\"u}hn, 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.",

author = "Jordi Guiu and Edouard Hannezo and Shiro Yui and Samuel Demharter and Svetlana Ulyanchenko and Martti Maimets and Anne J{\o}rgensen and Signe Perlman and Lene Lundvall and Mamsen, {Linn Salto} and Agnete Larsen and Olesen, {Rasmus H} and Andersen, {Claus Yding} and Thuesen, {Lea Langhoff} and Hare, {Kristine Juul} and Pers, {Tune H} and Konstantin Khodosevich and Simons, {Benjamin D} and Jensen, {Kim B}",

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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 - 2019/6/6

Y1 - 2019/6/6

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.

U2 - 10.1038/s41586-019-1212-5

DO - 10.1038/s41586-019-1212-5

M3 - Letter

C2 - 31092921

SN - 0028-0836

VL - 570

SP - 107

EP - 111

JO - Nature

JF - Nature

IS - 7759

ER -

Tracing the origin of adult intestinal stem cells

Abstract

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