Gene expression profiles of human cervical primary cells from ecto- and endocervix. Homo sapiens

The cellular origin of cervical cancers remains unclear. Revealing molecular details of transformation in this tissue has been hampered by the lack of culture systems, resembling the in vivo cervical architecture. Here we established a long-term in vitro 3D cervical organoid model derived from stem cells of human or mouse cervical tissue which recapitulates the in vivo stratified ectocervical and columnar endocervical epithelium. Stratified and columnar cervical epithelia arise from two discrete unipotent stem cell populations of the endocervix. Unique stem cell signatures reveal a dependency on intrinsic Notch and Wnt microenvironmental signals. The genetic signatures of KRT5+ stratified vs KRT7+ columnar cervical cells establish discrete groups of cervical cancer of the squamous and adenocarcinoma types, respectively. Cervical tissue morphology is guided by the interplay of two discrete unipotent cervical stem cell populations and the spatio-temporal distribution of signals from the stroma. Overall design: Primary cells were isolated from healthy tissue of surgery specimen taken from ecto and/or endocervix of patients undergoing hysterectomy or cononization, cultured in 2D, transferred to Matrigel and cultured for 3d or 2weeks. Total RNA was extracted from samples and hybridized on Agilent-8x60k Human custom arrays as single-color hybridizations.