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.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3370, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Forster
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3370, USA.
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Chiba
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3370, USA.
authors.forename: Lorian
authors.initials: L
authors.lastname: Schaeffer
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3370, USA.
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Regalado
authors.affiliation: The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Christine S
authors.initials: CS
authors.lastname: Lai
authors.affiliation: The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Gao
authors.affiliation: The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Samira
authors.initials: S
authors.lastname: Kiani
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, University Medical Center Utrecht, 3584 Utrecht, the Netherlands.
authors.forename: Henner F
authors.initials: HF
authors.lastname: Farin
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, University Medical Center Utrecht, 3584 Utrecht, the Netherlands ; Skolkovo Institute of Science and Technology (Skoltech), Novaya str. 100, Skolkovo, Moscow Region 143025, Russia.
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
authors.affiliation: Sangamo BioSciences, Richmond, CA 94804, USA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Cost
authors.affiliation: Sangamo BioSciences, Richmond, CA 94804, USA.
authors.forename: Andy
authors.initials: A
authors.lastname: Chan
authors.affiliation: Sangamo BioSciences, Richmond, CA 94804, USA.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Rebar
authors.affiliation: Sangamo BioSciences, Richmond, CA 94804, USA.
authors.forename: Fyodor D
authors.initials: FD
authors.lastname: Urnov
authors.affiliation: Sangamo BioSciences, Richmond, CA 94804, USA.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Gregory
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3370, USA ; Department of Mathematics and Computer Science, University of California, Berkeley, Berkeley, CA 94720-3840, USA.
authors.forename: Lior
authors.initials: L
authors.lastname: Pachter
authors.affiliation: The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA ; Skolkovo Institute of Science and Technology (Skoltech), Novaya str. 100, Skolkovo, Moscow Region 143025, Russia ; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Jaenisch
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3370, USA.
authors.forename: Dirk
authors.initials: D
authors.lastname: Hockemeyer
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism*; D002478:Cells, Cultured; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007422:Intestines / Q000166:cytology*; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
chemical_list: C116884:LGR5 protein, human; D043562:Receptors, G-Protein-Coupled