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- Title
Paneth-like cells produced from OLFM4<sup>+</sup> stem cells support OLFM4<sup>+</sup> stem cell growth in advanced colorectal cancer.
- Authors
Sakahara, Mizuho; Okamoto, Takuya; Srivastava, Upasna; Natsume, Yasuko; Yamanaka, Hitomi; Suzuki, Yutaka; Obama, Kazutaka; Nagayama, Satoshi; Yao, Ryoji
- Abstract
Tumor tissues consist of heterogeneous cells that originate from stem cells; however, their cell fate determination program remains incompletely understood. Using patient-derived organoids established from patients with advanced colorectal cancer (CRC), we evaluated the potential of olfactomedin 4 (OLFM4)+ stem cells to produce a bifurcated lineage of progenies with absorptive and secretory properties. In the early phases of organoid reconstruction, OLFM4+ cells preferentially gave rise to secretory cells. Additionally, we found that Paneth-like cells, which do not exist in the normal colon, were induced in response to Notch signaling inhibition. Video recordings of single OLFM4+ cells revealed that organoids containing Paneth-like cells were effectively propagated and that their selective ablation led to organoid collapse. In tumor tissues, Paneth-like cells were identified only in the region where tumor cells lost cell adhesion. These findings indicate that Paneth-like cells are directly produced by OLFM4+ stem cells and that their interaction contributes to tumor formation by providing niche factors. This study reveals the importance of the cell fate specification program for building a complete tumor cellular ecosystem, which might be targeted with novel therapeutics. An analysis of the reconstitution process of orgenoids revelaed that OLFM4+ cells in colorectal cancer directrly generate Paneth-like cells, which supported OLFM4+ cells growth by providing niche.
- Subjects
STEM cells; COLORECTAL cancer; CELL differentiation; CELL determination; CELL growth; NOTCH genes; CELL adhesion
- Publication
Communications Biology, 2024, Vol 7, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-023-05504-8