Long-term organoid culture reveals enrichment of organoid-forming epithelial cells in the fimbrial portion of mouse fallopian tube
A recent paradigm shift in ovarian cancer research is the finding that many ovarian cancers may originate from fallopian tube epithelial (FTE) cells. As tissue stem and progenitor cells often serve as cells of origin of cancer, a better understanding of FTE stem/progenitor cells and how they become...
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doaj-cda9f45913de4bf08f72e611f09cbc6f2020-11-25T00:44:39ZengElsevierStem Cell Research1873-50612018-10-01325160Long-term organoid culture reveals enrichment of organoid-forming epithelial cells in the fimbrial portion of mouse fallopian tubeYing Xie0Eun-Sil Park1Dongxi Xiang2Zhe Li3Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA; Life Sciences Institute of Guangxi Medical University, Nanning, Guangxi, 530021, PR China.; Key Laboratory of High-Incident-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, 530021, PR China.Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USADivision of Genetics, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USADivision of Genetics, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA; Corresponding author at: Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.A recent paradigm shift in ovarian cancer research is the finding that many ovarian cancers may originate from fallopian tube epithelial (FTE) cells. As tissue stem and progenitor cells often serve as cells of origin of cancer, a better understanding of FTE stem/progenitor cells and how they become transformed is essential for early detection and prevention of ovarian cancer. To facilitate study of FTE stem/progenitor cells in model systems, we established an organoid culture system for mouse FTE cells. We find that EPCAM+ mouse FTE cells can be stably cultured long-term under a minimal condition of activated EGF signaling and suppressed TGFbeta signaling. We show that both Notch and Wnt signaling are required for growth of FTE cells in organoids, and further activation of Wnt signaling supports their maturation toward the ciliated cell lineage. Lastly, by analyzing the frequency of organoid-forming cells in different portions of the fallopian tube (FT), we find that the distal portion of the FT, which includes the fimbria, is enriched with organoid-forming FTE stem cells. Keywords: Fallopian tube epithelial cell, Oviduct, Organoid culture, Tissue stem cell, Fimbria, Cellular origin of ovarian cancerhttp://www.sciencedirect.com/science/article/pii/S1873506118302149 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ying Xie Eun-Sil Park Dongxi Xiang Zhe Li |
spellingShingle |
Ying Xie Eun-Sil Park Dongxi Xiang Zhe Li Long-term organoid culture reveals enrichment of organoid-forming epithelial cells in the fimbrial portion of mouse fallopian tube Stem Cell Research |
author_facet |
Ying Xie Eun-Sil Park Dongxi Xiang Zhe Li |
author_sort |
Ying Xie |
title |
Long-term organoid culture reveals enrichment of organoid-forming epithelial cells in the fimbrial portion of mouse fallopian tube |
title_short |
Long-term organoid culture reveals enrichment of organoid-forming epithelial cells in the fimbrial portion of mouse fallopian tube |
title_full |
Long-term organoid culture reveals enrichment of organoid-forming epithelial cells in the fimbrial portion of mouse fallopian tube |
title_fullStr |
Long-term organoid culture reveals enrichment of organoid-forming epithelial cells in the fimbrial portion of mouse fallopian tube |
title_full_unstemmed |
Long-term organoid culture reveals enrichment of organoid-forming epithelial cells in the fimbrial portion of mouse fallopian tube |
title_sort |
long-term organoid culture reveals enrichment of organoid-forming epithelial cells in the fimbrial portion of mouse fallopian tube |
publisher |
Elsevier |
series |
Stem Cell Research |
issn |
1873-5061 |
publishDate |
2018-10-01 |
description |
A recent paradigm shift in ovarian cancer research is the finding that many ovarian cancers may originate from fallopian tube epithelial (FTE) cells. As tissue stem and progenitor cells often serve as cells of origin of cancer, a better understanding of FTE stem/progenitor cells and how they become transformed is essential for early detection and prevention of ovarian cancer. To facilitate study of FTE stem/progenitor cells in model systems, we established an organoid culture system for mouse FTE cells. We find that EPCAM+ mouse FTE cells can be stably cultured long-term under a minimal condition of activated EGF signaling and suppressed TGFbeta signaling. We show that both Notch and Wnt signaling are required for growth of FTE cells in organoids, and further activation of Wnt signaling supports their maturation toward the ciliated cell lineage. Lastly, by analyzing the frequency of organoid-forming cells in different portions of the fallopian tube (FT), we find that the distal portion of the FT, which includes the fimbria, is enriched with organoid-forming FTE stem cells. Keywords: Fallopian tube epithelial cell, Oviduct, Organoid culture, Tissue stem cell, Fimbria, Cellular origin of ovarian cancer |
url |
http://www.sciencedirect.com/science/article/pii/S1873506118302149 |
work_keys_str_mv |
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