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bioRxiv · 10.1101/2021.10.21.465257

Spatial transcriptomics reveals the two cancer stem cell-like populations in triple-negative breast cancer

Nakayama, J.·Matsunaga, H.·Arikawa, K.·Yoda, T.·Hosokawa, M.·Takeyama, H.·Yamamoto, Y.·Semba, K.
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Abstract

Gene expression analysis at the single-cell level by next generation sequencing has revealed the existence of clonal dissemination and microheterogeneity in cancer metastasis. The current spatial analysis technologies can elucidate the heterogeneity of cell-cell interactions in situ. To reveal the regional and expressional heterogeneity in primary tumors and metastases, we performed transcriptomic analysis of microtissues dissected from a triple-negative breast cancer (TNBC) cell line MDA-MB-231 xenograft model with our automated tissue microdissection punching technology. This multiple-microtissue transcriptome analysis revealed three cancer cell-type clusters in the primary tumor and axillary lymph node metastasis, two of which were cancer stem cell (CSC)-like clusters (CD44/MYC-high, HMGA1-high). Reanalysis of public single-cell RNA-seq (scRNA-seq) datasets confirmed that the two CSC-like populations existed both in TNBC xenograft models and TNBC patients. In addition, the gene signature of the HMGA1-high CSC-like cluster has the potential to serve as a novel biomarker for diagnosis. The diversity of these multiple CSC-like populations may cause differential anticancer drug resistance, increasing the difficulty of curing this cancer.

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Nakayama, J., Matsunaga, H., Arikawa, K., Yoda, T., Hosokawa, M., Takeyama, H., Yamamoto, Y., Semba, K.. 2021-10-21. Spatial transcriptomics reveals the two cancer stem cell-like populations in triple-negative breast cancer. https://doi.org/10.1101/2021.10.21.465257

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