Korean Biological research group in Michigan

KBM은 미시간에서 의학, 약학, 생물학 관련 연구를 수행하는 연구자들간의 시너지를 도모하는 모임 입니다.

매달 학술 세미나 및 네트워킹 세션을 진행 하고 있으며, 미시간에 계시는 모든 연구자들의 참여를 환영합니다.



KBM is first organized by a group of researchers from the University of Michigan working in various bio-related fields. Since 2020, we have been having regular seminars and network sessions through an online platform. We believe now is the right timing for expanding our group beyond the Michigan area. So if you are interested in joining the seminars and meetings, please contact us!

Contact: kbm.president@gmail.com

Murine Prostate Luminal Epithelial Diversity Captured by Single Cell RNA Sequencing

Abstract

Prostate cancer is one of the leading causes of cancer-related mortality among the aging western male population. Previous seminal studies have characterized the distinct molecular driver aberrations in prostate cancers including, the recurrent ETS gene fusions, SPOP mutations, PTEN copy loss among others in prostatic adenocarcinoma, and NMYC gene amplification among the neuroendocrine prostate cancers. TCGA flagship study that characterized 333 primary localized prostate cancer patient (predominantly Caucasian population) samples, revealed several distinct molecular subtypes, that include ETS gene fusions (~60%), SPOP mutant (11%) other (long tail, heterogeneous class 26%). PTEN loss was noted in 17% of the cases and mainly co-occurred with ETS gene fusions. While ETS gene fusions were sufficient to drive human prostate cancer, replicating this aberration in mouse luminal epithelial cells produced only pre-cancerous mouse prostatic intraepithelial neoplasia (mPIN) and not the full disease. In the murine model loss of PTEN was essential to drive the neoplasm and hence existing genetically engineered prostate cancer murine models such as HIMYC and PTEN-null models have several limitations. They lack faithful representation of the human disease, in terms of disease initiation, progression, and comprehensive molecular driver aberrations. Unlike the human prostate gland, the murine equivalent is multilobulated and hence we hypothesize that murine prostate luminal epithelial cells may have lobe specific epithelial cell diversity and a comparative study of the transcriptional programs that occur in human and murine prostate luminal epithelial cells will help identify the appropriate cell type that can be transformed by human PCa molecular drivers.