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Direct Lineage Reprogramming of Mouse Fibroblasts to Acquire the Identity of Fetal Intestine-Derived Progenitor Cells
Shizuka Miura1, Atsushi Suzuki2
1Division of Organogenesis and Regeneration, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Methods in Molecular Biology (Clifton, N.J.)
|July 25, 2020
Summary
Researchers developed a new method to create intestinal organoids from fibroblasts, bypassing the need for donor tissue or stem cells. This breakthrough offers a novel source for studying intestinal diseases and advancing regenerative therapies.
Area of Science:
- Gastroenterology and Regenerative Medicine
- Stem Cell Biology
- Developmental Biology
Background:
- Intestinal organoids are valuable models for studying intestinal diseases and treatments.
- Current methods for generating intestinal organoids rely on donor tissue or pluripotent stem cells, limiting their accessibility.
- A new, more accessible source for intestinal organoid generation is needed.
Purpose of the Study:
- To establish a novel method for generating intestinal organoids from fibroblasts.
- To investigate the potential of induced progenitor and stem cells derived from fibroblasts.
- To assess the utility of these novel organoids in disease modeling and regenerative therapy.
Main Methods:
- Direct reprogramming of mouse embryonic fibroblasts (MEFs) into fetal intestine-derived progenitor cells (FIPCs).
- Generation of induced intestinal stem cells (iISCs) from induced FIPCs (iFIPCs).
- Culture of iFIPCs and iISCs to form intestinal organoids.
Main Results:
- Successfully reprogrammed MEFs into iFIPCs with progenitor cell properties.
- Induced iFIPCs differentiated into iISCs, resembling native intestinal stem cells.
- Both iFIPCs and iISCs formed organoids comparable to those derived from native cells.
- The generated organoids exhibited characteristics suitable for disease study and regenerative applications.
Conclusions:
- Fibroblasts can be reprogrammed to generate functional intestinal organoids.
- This novel approach expands the sources for intestinal organoid generation.
- Induced intestinal organoids hold promise for advancing intestinal disease research and regenerative medicine.
