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

Research output: Contribution to journalArticle

58 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 languageEnglish (US)
Pages (from-to)838-852
Number of pages15
JournalStem Cell Reports
Volume2
Issue number6
DOIs
StatePublished - Jun 3 2014
Externally publishedYes

Fingerprint

Pluripotent Stem Cells
Adult Stem Cells
Stem cells
Tissue
Organoids
Biopsy
Cell culture
Intestinal Diseases
Intestines
Stem Cells
Transplantation
Chemical analysis

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

Cite this

Forster, R., Chiba, K., Schaeffer, L., Regalado, S. G., Lai, C. S., Gao, Q., ... Hockemeyer, D. (2014). Human intestinal tissue with adult stem cell properties derived from pluripotent stem cells. Stem Cell Reports, 2(6), 838-852. https://doi.org/10.1016/j.stemcr.2014.05.001

Human intestinal tissue with adult stem cell properties derived from pluripotent stem cells. / Forster, Ryan; Chiba, Kunitoshi; Schaeffer, Lorian; Regalado, Samuel G.; Lai, Christine S.; Gao, Qing; Kiani, Samira; Farin, Henner F.; Clevers, Hans; Cost, Gregory J.; Chan, Andy; Rebar, Edward J.; Urnov, Fyodor D.; Gregory, Philip D.; Pachter, Lior; Jaenisch, Rudolf; Hockemeyer, Dirk.

In: Stem Cell Reports, Vol. 2, No. 6, 03.06.2014, p. 838-852.

Research output: Contribution to journalArticle

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. 838-852. https://doi.org/10.1016/j.stemcr.2014.05.001
Forster, Ryan ; Chiba, Kunitoshi ; Schaeffer, Lorian ; Regalado, Samuel G. ; Lai, Christine S. ; Gao, Qing ; Kiani, Samira ; Farin, Henner F. ; Clevers, Hans ; Cost, Gregory J. ; Chan, Andy ; Rebar, Edward J. ; Urnov, Fyodor D. ; Gregory, Philip D. ; Pachter, Lior ; Jaenisch, Rudolf ; Hockemeyer, Dirk. / Human intestinal tissue with adult stem cell properties derived from pluripotent stem cells. In: Stem Cell Reports. 2014 ; Vol. 2, No. 6. pp. 838-852.
@article{15399bf8205045d4be4e90c044cc9e6a,
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",
year = "2014",
month = "6",
day = "3",
doi = "10.1016/j.stemcr.2014.05.001",
language = "English (US)",
volume = "2",
pages = "838--852",
journal = "Stem Cell Reports",
issn = "2213-6711",
publisher = "Cell Press",
number = "6",

}

TY - JOUR

T1 - Human intestinal tissue with adult stem cell properties derived from pluripotent stem cells

AU - Forster, Ryan

AU - Chiba, Kunitoshi

AU - Schaeffer, Lorian

AU - Regalado, Samuel G.

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

PY - 2014/6/3

Y1 - 2014/6/3

N2 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=84902144564&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902144564&partnerID=8YFLogxK

U2 - 10.1016/j.stemcr.2014.05.001

DO - 10.1016/j.stemcr.2014.05.001

M3 - Article

VL - 2

SP - 838

EP - 852

JO - Stem Cell Reports

JF - Stem Cell Reports

SN - 2213-6711

IS - 6

ER -