James M. Wells - Cincinnati OH, US Jason R. Spence - Cincinnati OH, US Aaron M. Zorn - Cincinnati OH, US Noah F. Shroyer - Cincinnati OH, US
Assignee:
CHILDREN'S HOSPITAL MEDICAL CENTER - Cincinnati OH
International Classification:
C12N 5/071
US Classification:
435 29, 435377
Abstract:
The generation of complex organ tissues from human embryonic and pluripotent stem cells (PSCs) remains a major challenge for translational studies. It is shown that PSCs can be directed to differentiate into intestinal tissue in vitro by modulating the combinatorial activities of several signaling pathways in a step-wise fashion, effectively recapitulating in vivo fetal intestinal al development. The resulting intestinal “organoids” were three-dimensional structures consisting of a polarized, columnar epithelium surrounded by mesenchyme that included a smooth muscle-like layer. The epithelium was patterned into crypt-like SOX9-positive proliferative zones and villus-like structures with all of the major functional cell types of the intestine. The culture system is used to demonstrate that expression of NEUROG3, a pro-endocrine transcription factor mutated in enteric anendocrinosis is sufficient to promote differentiation towards the enteroendocrine cell lineage. In conclusion, PSC-derived human intestinal tissue should allow for unprecedented studies of human intestinal development, homeostasis and disease.
- Ann Arbor MI, US Emily Holloway - Ann Arbor MI, US Jason Spence - Ann Arbor MI, US
International Classification:
C12N 5/071 G01N 33/50
Abstract:
The invention disclosed herein generally relates to methods and systems for improving physiological growth of cultured tissues. In particular, the invention disclosed herein relates to methods and systems for promoting maintenance of cultured intestinal organoids (e.g., derived from pluripotent stem cells or from primary sources such as biopsy tissue).
Compositions And Methods For Obtaining Vascularized Human Intestinal Organoid Tissue, And Related Uses Thereof
- Ann Arbor MI, US Jason Spence - Ann Arbor MI, US
International Classification:
C12N 5/071
Abstract:
The invention disclosed herein generally relates to methods and systems for converting stem cells into specific tissue(s) or organ(s) through directed differentiation. In particular, the invention disclosed herein relates to methods and systems for promoting vascularized human intestinal organoid tissue having an intestine-specific EC transcriptional signature from hindgut spheroid tissue produced in vitro from the described methods.
Methods And Systems For Converting Precursor Cells Into Intestinal Tissues Through Directed Differentiation
- Cincinnati OH, US Aaron M. Zorn - Cincinnati OH, US Jason R. Spence - Ann Arbor MI, US Noah F. Shroyer - Houston TX, US
International Classification:
C12N 5/071 C12N 5/077
Abstract:
The generation of complex organ tissues from human embryonic and pluripotent stem cells (PSCs) remains a major challenge for translational studies. It is shown that PSCs can be directed to differentiate into intestinal tissue in vitro by modulating the combinatorial activities of several signaling pathways in a step-wise fashion, effectively recapitulating in vivo fetal intestinal development. The resulting intestinal “organoids” were three-dimensional structures consisting of a polarized, columnar epithelium surrounded by mesenchyme that included a smooth muscle-like layer. The epithelium was patterned into crypt-like SOX9-positive proliferative zones and villus-like structures with all of the major functional cell types of the intestine. The culture system is used to demonstrate that expression of NEUROG3, a pro-endocrine transcription factor mutated in enteric anendocrinosis is sufficient to promote differentiation towards the enteroendocrine cell lineage. In conclusion, PSC-derived human intestinal tissue should allow for unprecedented studies of human intestinal development, homeostasis and disease.
Synthetic Hydrogel Carriers For Cellular Structures, Generation Of Organoids, And Treatment Of Tissue Injury
- Cincinnati OH, US Aaron M. Zorn - Cincinnati OH, US Jason R. Spence - Ann Arbor MI, US Noah F. Shroyer - Houston TX, US
International Classification:
C12N 5/071 C12N 5/077
Abstract:
The generation of complex organ tissues from human embryonic and pluripotent stem cells (PSCs) remains a major challenge for translational studies. It is shown that PSCs can be directed to differentiate into intestinal tissue in vitro by modulating the combinatorial activities of several signaling pathways in a step-wise fashion, effectively recapitulating in vivo fetal intestinal development. The resulting intestinal “organoids” were three-dimensional structures consisting of a polarized, columnar epithelium surrounded by mesenchyme that included a smooth muscle-like layer. The epithelium was patterned into crypt-like SOX9-positive proliferative zones and villus-like structures with all of the major functional cell types of the intestine. The culture system is used to demonstrate that expression of NEUROG3, a pro-endocrine transcription factor mutated in enteric anendocrinosis is sufficient to promote differentiation towards the enteroendocrine cell lineage. In conclusion, PSC-derived human intestinal tissue should allow for unprecedented studies of human intestinal development, homeostasis and disease.
University of Michigan
Associate Professor
University of Michigan Medical School Oct 2011 - Aug 2016
Assistant Professor at University of Michigan Medical School
Cincinnati Children's Hospital Medical Center Oct 2006 - Sep 2011
Research Fellow
Education:
Miami University 2001 - 2006
Doctorates, Doctor of Philosophy, Molecular Biology, Philosophy
Canisius College 1997 - 2001
Bachelors, Bachelor of Science, Biology
Skills:
Stem Cells Developmental Biology Science Molecular Biology Cell Biology Scientific Writing Regenerative Medicine Research Stem Cell Technology Project Management Problem Solving Collaborative Problem Solving Experimentation Experimental Design Experimental Analysis Biology Embryonic Stem Cells Stem Cell Research Adult Stem Cells
Interests:
Developmental Biology Science Human Pluripotent Stem Cells Regenerative Medicine Lungs Intestines
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