Integrating spatial and single-cell multi-omics analysis of induced pluripotent stem cell-derived cervical adenocarcinoma model

Saki Kamata; Ayumi Taguchi; Hitoshi Iuchi; Yuji Ikeda; Rie Maruyama; Yoko Nakanishi; Toshihiro Sugi; Yuki Okuma; Osamu Kobayashi; Naoko Tomita; Daisuke Yoshimoto; Lifang Wang; Nozomi Moritsugu; Chitose Takahashi; Michihira Tagami; Hiroko Matsunaga; Toshitsugu Okayama; Ri-ichiroh Manabe; Kazuma Kiyotani; Kazuho Ikeo; Yasushi Okazaki; Tohru Kiyono; Shinobu Masuda; Michiaki Hamada; Haruko Takeyama; Kei Kawana

doi:10.64898/2026.05.01.722143

Cancer BiologybioRxivMay 6, 2026

Preprint

Integrating spatial and single-cell multi-omics analysis of induced pluripotent stem cell-derived cervical adenocarcinoma model

Saki Kamata iD, Ayumi Taguchi, Hitoshi Iuchi iD, Yuji Ikeda iD, Rie Maruyama, Yoko Nakanishi iD, Toshihiro Sugi, Yuki Okuma iD, Osamu Kobayashi iD, Naoko Tomita, Daisuke Yoshimoto iD, Lifang Wang iD, Nozomi Moritsugu, Chitose Takahashi iD, Michihira Tagami iD, Hiroko Matsunaga iD, Toshitsugu Okayama, Ri-ichiroh Manabe, Kazuma Kiyotani iD, Kazuho Ikeo iD, Yasushi Okazaki iD, Tohru Kiyono iD, Shinobu Masuda iD, Michiaki Hamada iD, Haruko Takeyama iD, Kei Kawana iD

Abstract

Human papillomavirus 18 (HPV18) preferentially infects cervical stem cell-like cells and is strongly associated with adenocarcinoma. However, the mechanisms underlying differentiation into cervical adenocarcinoma remain unclear due to the lack of appropriate experimental models. We aimed to establish a model of HPV18-associated cervical adenocarcinoma and elucidate its molecular and cellular differentiation mechanisms. HPV18 E6/E7 were introduced into induced pluripotent stem cell-derived reserve cell-like cells (iRCs) to generate tumor models. Spatial transcriptomics and single-cell multi-omics analyses were performed to integrate histological and molecular data. A distinct component (Gland_A) exhibited morphological and immunohistochemical features of cervical adenocarcinoma and was efficiently induced in iRC-18 tumors. Gland_A showed increased chromatin accessibility and elevated expression of FOXA1, FOXA2, and ALDH1A1. Analysis of clinical samples confirmed enrichment of ALDH1A1 in HPV-associated adenocarcinomas. This model recapitulates key features of HPV18-associated cervical adenocarcinoma and provides insights into its differentiation mechanisms.

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