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

Stem Cell Reports (Jun 2014)

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

Affiliations

Ryan Forster: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3370, USA
Kunitoshi Chiba: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3370, USA
Lorian Schaeffer: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3370, USA
Samuel G. Regalado: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3370, USA
Christine S. Lai: The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
Qing Gao: The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
Samira Kiani: The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
Henner F. Farin: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, University Medical Center Utrecht, 3584 Utrecht, the Netherlands
Hans Clevers: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, University Medical Center Utrecht, 3584 Utrecht, the Netherlands
Gregory J. Cost: Sangamo BioSciences, Richmond, CA 94804, USA
Andy Chan: Sangamo BioSciences, Richmond, CA 94804, USA
Edward J. Rebar: Sangamo BioSciences, Richmond, CA 94804, USA
Fyodor D. Urnov: Sangamo BioSciences, Richmond, CA 94804, USA
Philip D. Gregory: Sangamo BioSciences, Richmond, CA 94804, USA
Lior Pachter: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3370, USA
Rudolf Jaenisch: The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
Dirk Hockemeyer: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3370, USA

DOI: https://doi.org/10.1016/j.stemcr.2014.05.001
Journal volume & issue: Vol. 2, no. 6
pp. 838 – 852

Abstract

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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.

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

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