@article{KosterGurumurthyKumaretal.2022, author = {Koster, Stefanie and Gurumurthy, Rajendra Kumar and Kumar, Naveen and Prakash, Pon Ganish and Dhanraj, Jayabhuvaneshwari and Bayer, Sofia and Berger, Hilmar and Kurian, Shilpa Mary and Drabkina, Marina and Mollenkopf, Hans-Joachim and Goosmann, Christian and Brinkmann, Volker and Nagel, Zachary and Mangler, Mandy and Meyer, Thomas F. and Chumduri, Cindrilla}, title = {Modelling Chlamydia and HPV co-infection in patient-derived ectocervix organoids reveals distinct cellular reprogramming}, series = {Nature Communications}, volume = {13}, journal = {Nature Communications}, number = {1}, doi = {10.1038/s41467-022-28569-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301349}, year = {2022}, abstract = {Coinfections with pathogenic microbes continually confront cervical mucosa, yet their implications in pathogenesis remain unclear. Lack of in-vitro models recapitulating cervical epithelium has been a bottleneck to study coinfections. Using patient-derived ectocervical organoids, we systematically modeled individual and coinfection dynamics of Human papillomavirus (HPV)16 E6E7 and Chlamydia, associated with carcinogenesis. The ectocervical stem cells were genetically manipulated to introduce E6E7 oncogenes to mimic HPV16 integration. Organoids from these stem cells develop the characteristics of precancerous lesions while retaining the self-renewal capacity and organize into mature stratified epithelium similar to healthy organoids. HPV16 E6E7 interferes with Chlamydia development and induces persistence. Unique transcriptional and post-translational responses induced by Chlamydia and HPV lead to distinct reprogramming of host cell processes. Strikingly, Chlamydia impedes HPV-induced mechanisms that maintain cellular and genome integrity, including mismatch repair in the stem cells. Together, our study employing organoids demonstrates the hazard of multiple infections and the unique cellular microenvironment they create, potentially contributing to neoplastic progression.}, language = {en} } @article{ChumduriTurco2021, author = {Chumduri, Cindrilla and Turco, Margherita Y.}, title = {Organoids of the female reproductive tract}, series = {Journal of Molecular Medicine}, volume = {99}, journal = {Journal of Molecular Medicine}, number = {4}, doi = {10.1007/s00109-020-02028-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-328374}, pages = {531-553}, year = {2021}, abstract = {Healthy functioning of the female reproductive tract (FRT) depends on balanced and dynamic regulation by hormones during the menstrual cycle, pregnancy and childbirth. The mucosal epithelial lining of different regions of the FRT—ovaries, fallopian tubes, uterus, cervix and vagina—facilitates the selective transport of gametes and successful transfer of the zygote to the uterus where it implants and pregnancy takes place. It also prevents pathogen entry. Recent developments in three-dimensional (3D) organoid systems from the FRT now provide crucial experimental models that recapitulate the cellular heterogeneity and physiological, anatomical and functional properties of the organ in vitro. In this review, we summarise the state of the art on organoids generated from different regions of the FRT. We discuss the potential applications of these powerful in vitro models to study normal physiology, fertility, infections, diseases, drug discovery and personalised medicine.}, language = {en} }