Cited by 91Pluripotent Stem Cells ResearchCancer Cells and MetastasisDigestive system and related health

Generation of Mouse and Human Organoid-Forming Intestinal Progenitor Cells by Direct Lineage Reprogramming

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Miura, Shizuka, Suzuki, Atsushi·2017·Cell Stem Cell

Abstract

Intestinal organoids hold great promise as a valuable tool for studying and treating intestinal diseases. The currently available sources of human intestinal organoids, tissue fragments or pluripotent stem cells, involve invasive procedures or complex differentiation protocols, respectively. Here, we show that a set of four transcription factors, Hnf4α, Foxa3, Gata6, and Cdx2, can directly reprogram mouse fibroblasts to acquire the identity of fetal intestine-derived progenitor cells (FIPCs). These induced FIPCs (iFIPCs) form spherical organoids that develop into adult-type budding organoids containing cells with intestinal stem cell properties. The resulting stem cells produce all intestinal epithelial cell lineages and undergo self-renewing cell divisions. After transplantation, the induced spherical and budding organoids can reconstitute colonic and intestinal epithelia, respectively. The same combination of four defined transcription factors can also induce human iFIPCs. This alternative approach for producing intestinal organoids may well facilitate application for disease analysis and therapy development.

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Authors
Miura, S., & Suzuki, A.
Affiliations
Kyushu University (JP)
Corresponding author
Suzuki, Atsushi
Venue
Cell Stem Cell
Publisher
Elsevier BV
Published
2017-10
Volume
21
Issue
4
Pages
456-471.e5
ISSN
  • 1875-9777 (ISSN-L)
  • 1934-5909
OpenAlex
W2758459988
Cited by
91
References
40
Citations by year
2026: 5 · 2025: 10 · 2024: 12 · 2023: 14 · 2022: 11 · 2021: 14 · 2020: 12 · 2019: 4 · 2018: 8 · 2017: 1
FWCI
2.79
Type
journal article
Language
en
Open access
Locations
  • Cell stem cell (publishedVersion)
  • PubMed (publishedVersion)
  • Kyushu University Institutional Repository (QIR) (Kyushu University) (submittedVersion)
  • Institutional Repositories DataBase (IRDB) (submittedVersion)
Funders
  • Japan Society for the Promotion of Science (16H01850, 23112002, 25713014, FDG6J02459)
  • Ministry of Education, Culture, Sports, Science and Technology
  • Core Research for Evolutional Science and Technology
  • Japan Agency for Medical Research and Development
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
Keywords
intestinal organoids, intestinal progenitor cells, fibroblast reprogramming, transcription factors, HNF4α, FOXA3, GATA6, CDX2, intestinal stem cells, organoid transplantation, self-renewal, human organoids
MeSH terms
Cell Self Renewal, Animals, Colon, Embryo, Mammalian, Fetus, Fibroblasts, Humans, Intestinal Mucosa, Intestines, Organoids, Regeneration, Stem Cells, Transcription Factors, Spheroids, Cellular, Cell Lineage, Transgenes, Gene Silencing, Stem Cell Transplantation, Receptors, G-Protein-Coupled, Tissue Culture Techniques, Cell Proliferation, Mice, Cellular Reprogramming

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