Human intestinal tissue with adult stem cell properties derived from pluripotent stem cells

Ryan Forster; Kunitoshi Chiba; Lorian Schaeffer; Samuel G Regalado; Christine S Lai; Qing Gao; Samira Kiani; Henner F Farin; Hans Clevers; Gregory J Cost; Andy Chan; Edward J Rebar; Fyodor D Urnov; Philip D Gregory; Lior Pachter; Rudolf Jaenisch; Dirk Hockemeyer

doi:10.1016/j.stemcr.2014.05.001

Human intestinal tissue with adult stem cell properties derived from pluripotent stem cells

Ryan Forster, Kunitoshi Chiba, Lorian Schaeffer, Samuel G Regalado, Christine S Lai, Qing Gao, Samira Kiani, Henner F Farin, Hans Clevers, Gregory J Cost, Andy Chan, Edward J Rebar, Fyodor D Urnov, Philip D Gregory, Lior Pachter, Rudolf Jaenisch, Dirk Hockemeyer

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

79 Citations (Scopus)

Abstract

Genetically engineered human pluripotent stem cells (hPSCs) have been proposed as a source for transplantation therapies and are rapidly becoming valuable tools for human disease modeling. However, many applications are limited due to the lack of robust differentiation paradigms that allow for the isolation of defined functional tissues. Here, using an endogenous LGR5-GFP reporter, we derived adult stem cells from hPSCs that gave rise to functional human intestinal tissue comprising all major cell types of the intestine. Histological and functional analyses revealed that such human organoid cultures could be derived with high purity and with a composition and morphology similar to those of cultures obtained from human biopsies. Importantly, hPSC-derived organoids responded to the canonical signaling pathways that control self-renewal and differentiation in the adult human intestinal stem cell compartment. This adult stem cell system provides a platform for studying human intestinal disease in vitro using genetically engineered hPSCs.

Original language	English
Pages (from-to)	838-52
Number of pages	15
Journal	Stem Cell Reports
Volume	2
Issue number	6
DOIs	https://doi.org/10.1016/j.stemcr.2014.05.001
Publication status	Published - 03 Jun 2014

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Forster, R., Chiba, K., Schaeffer, L., Regalado, S. G., Lai, C. S., Gao, Q., Kiani, S., Farin, H. F., Clevers, H., Cost, G. J., Chan, A., Rebar, E. J., Urnov, F. D., Gregory, P. D., Pachter, L., Jaenisch, R., & Hockemeyer, D. (2014). Human intestinal tissue with adult stem cell properties derived from pluripotent stem cells. Stem Cell Reports, 2(6), 838-52. https://doi.org/10.1016/j.stemcr.2014.05.001

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title = "Human intestinal tissue with adult stem cell properties derived from pluripotent stem cells",

abstract = "Genetically engineered human pluripotent stem cells (hPSCs) have been proposed as a source for transplantation therapies and are rapidly becoming valuable tools for human disease modeling. However, many applications are limited due to the lack of robust differentiation paradigms that allow for the isolation of defined functional tissues. Here, using an endogenous LGR5-GFP reporter, we derived adult stem cells from hPSCs that gave rise to functional human intestinal tissue comprising all major cell types of the intestine. Histological and functional analyses revealed that such human organoid cultures could be derived with high purity and with a composition and morphology similar to those of cultures obtained from human biopsies. Importantly, hPSC-derived organoids responded to the canonical signaling pathways that control self-renewal and differentiation in the adult human intestinal stem cell compartment. This adult stem cell system provides a platform for studying human intestinal disease in vitro using genetically engineered hPSCs.",

author = "Ryan Forster and Kunitoshi Chiba and Lorian Schaeffer and Regalado, {Samuel G} and Lai, {Christine S} and Qing Gao and Samira Kiani and Farin, {Henner F} and Hans Clevers and Cost, {Gregory J} and Andy Chan and Rebar, {Edward J} and Urnov, {Fyodor D} and Gregory, {Philip D} and Lior Pachter and Rudolf Jaenisch and Dirk Hockemeyer",

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Forster, R, Chiba, K, Schaeffer, L, Regalado, SG, Lai, CS, Gao, Q, Kiani, S, Farin, HF, Clevers, H, Cost, GJ, Chan, A, Rebar, EJ, Urnov, FD, Gregory, PD, Pachter, L, Jaenisch, R & Hockemeyer, D 2014, 'Human intestinal tissue with adult stem cell properties derived from pluripotent stem cells', Stem Cell Reports, vol. 2, no. 6, pp. 838-52. https://doi.org/10.1016/j.stemcr.2014.05.001

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AU - Chiba, Kunitoshi

AU - Schaeffer, Lorian

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AU - Lai, Christine S

AU - Gao, Qing

AU - Kiani, Samira

AU - Farin, Henner F

AU - Clevers, Hans

AU - Cost, Gregory J

AU - Chan, Andy

AU - Rebar, Edward J

AU - Urnov, Fyodor D

AU - Gregory, Philip D

AU - Pachter, Lior

AU - Jaenisch, Rudolf

AU - Hockemeyer, Dirk

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AB - Genetically engineered human pluripotent stem cells (hPSCs) have been proposed as a source for transplantation therapies and are rapidly becoming valuable tools for human disease modeling. However, many applications are limited due to the lack of robust differentiation paradigms that allow for the isolation of defined functional tissues. Here, using an endogenous LGR5-GFP reporter, we derived adult stem cells from hPSCs that gave rise to functional human intestinal tissue comprising all major cell types of the intestine. Histological and functional analyses revealed that such human organoid cultures could be derived with high purity and with a composition and morphology similar to those of cultures obtained from human biopsies. Importantly, hPSC-derived organoids responded to the canonical signaling pathways that control self-renewal and differentiation in the adult human intestinal stem cell compartment. This adult stem cell system provides a platform for studying human intestinal disease in vitro using genetically engineered hPSCs.

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Human intestinal tissue with adult stem cell properties derived from pluripotent stem cells

Abstract

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