Stem cell technologies, especially patient‐specific, induced stem cell pluripotency and directed differentiation, hold great promise for changing the landscape of medical therapies. Proper exploitation of these methods may lead to personalized organ transplants, but to regenerate organs, it is necessary to develop methods for assembling differentiated cells into functional, organ‐level ... More
Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche.
AuthorsSato T,Vries RG,Snippert HJ,van de Wetering M,Barker N,Stange DE,van Es JH,Abo A,Kujala P,Peters PJ,Clevers H
JournalNature
PubMed ID19329995
The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. We have recently demonstrated the presence of about six cycling Lgr5(+) stem cells at the bottoms of small-intestinal crypts. Here we describe the establishment of long-term culture conditions under which single crypts undergo multiple crypt fission events, while ... More
In vitro generation of human pluripotent stem cell derived lung organoids.
Recent breakthroughs in 3-dimensional (3D) organoid cultures for many organ systems have led to new physiologically complex in vitro models to study human development and disease. Here, we report the step-wise differentiation of human pluripotent stem cells (hPSCs) (embryonic and induced) into lung organoids. By manipulating developmental signaling pathways hPSCs ... More
In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration.
AuthorsHuch M,Dorrell C,Boj SF,van Es JH,Li VS,van de Wetering M,Sato T,Hamer K,Sasaki N,Finegold MJ,Haft A,Vries RG,Grompe M,Clevers H
JournalNature
PubMed ID23354049
The Wnt target gene Lgr5 marks actively dividing stem cells in Wnt-driven, self-renewing tissues such as small intestine and colon(1), stomach(2) and hair follicles(3). A 3D culture system allows long-term clonal expansion of single Lgr5(+) stem cells into transplantable organoids that retain many characteristics of the original epithelial architecture(2, 4, ... More
Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics.
Esophageal adenocarcinoma (EAC) incidence is increasing while 5-year survival rates remain less than 15%. A lack of experimental models has hampered progress. We have generated clinically annotated EAC organoid cultures that recapitulate the morphology, genomic, and transcriptomic landscape of the primary tumor including point mutations, copy number alterations, and mutational ... More
Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro.
Studies in embryonic development have guided successful efforts to direct the differentiation of human embryonic and induced pluripotent stem cells (PSCs) into specific organ cell types in vitro 1,2. For example, human PSCs have been differentiated into monolayer cultures of liver hepatocytes and pancreatic endocrine cells3–6 that have therapeutic efficacy ... More
Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium.
AuthorsSato T,Stange DE,Ferrante M,Vries RG,Van Es JH,Van den Brink S,Van Houdt WJ,Pronk A,Van Gorp J,Siersema PD,Clevers H
JournalGastroenterology
PubMed ID21889923
Background & aims: We previously established long-term culture conditions under which single crypts or stem cells derived from mouse small intestine expand over long periods. The expanding crypts undergo multiple crypt fission events, simultaneously generating villus-like epithelial domains that contain all differentiated types of cells. We have adapted the culture ... More
A comprehensive protocol for efficient differentiation of human NPCs into electrically competent neurons.
Troglitazone suppresses c-Myc levels in human prostate cancer cells via a PPAR?-independent mechanism.
AuthorsAkinyeke TO, Stewart LV,
JournalCancer Biol Ther
PubMed ID21525782
'Troglitazone is a ligand for the peroxisome proliferator activated receptor gamma (PPAR?) that decreases growth of human prostate cancer cells in vitro and in vivo. However, the mechanism by which troglitazone reduces prostate cancer cell growth is not fully understood. To understand the signaling pathways involved in troglitazone-induced decreases in ... More