The Notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids

被引：364

作者：

Kessler, Mirjana ^{[1
]}

Hoffmann, Karen ^{[1
]}

Brinkmann, Volker ^{[2
]}

Thieck, Oliver ^{[1
]}

Jackisch, Susan ^{[1
]}

Toelle, Benjamin ^{[1
]}

Berger, Hilmar ^{[1
]}

Mollenkopf, Hans-Joachim ^{[3
]}

Mangler, Mandy ^{[4
]}

Sehouli, Jalid ^{[5
]}

Fotopoulou, Christina ^{[5
]}

Meyer, Thomas F. ^{[1
]}

机构：

[1] Max Planck Inst Infect Biol, Dept Mol Biol, D-10117 Berlin, Germany

[2] Max Planck Inst Infect Biol, Core Facil Microscopy, D-10117 Berlin, Germany

[3] Max Planck Inst Infect Biol, Core Facil Microarray, D-10117 Berlin, Germany

[4] Charite, Dept Gynecol, D-10117 Berlin, Germany

[5] Charite, Dept Gynecol, D-13353 Berlin, Germany

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

关键词：

OVARIAN-CANCER; HAIR FOLLICLE; CELLS; LGR5; EXPRESSION; PROTEINS; MUTATIONS; RECEPTORS; EXPANSION; COLON;

D O I：

10.1038/ncomms9989

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The epithelial lining of the fallopian tube is of critical importance for human reproduction and has been implicated as a site of origin of high-grade serous ovarian cancer. Here we report on the establishment of long-term, stable 3D organoid cultures from human fallopian tubes, indicative of the presence of adult stem cells. We show that single epithelial stem cells in vitro can give rise to differentiated organoids containing ciliated and secretory cells. Continuous growth and differentiation of organoids depend on both Wnt and Notch paracrine signalling. Microarray analysis reveals that inhibition of Notch signalling causes downregulation of stem cell-associated genes in parallel with decreased proliferation and increased numbers of ciliated cells and that organoids also respond to oestradiol and progesterone treatment in a physiological manner. Thus, our organoid model provides a much-needed basis for future investigations of signalling routes involved in health and disease of the fallopian tube.

引用

页数：11

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