Identifying cancer subtypes based on embryonic and hematopoietic stem cell signatures in pan-cancer.

PURPOSE: Cancer cells with stem cell-like properties may contribute to cancer development and therapy resistance. The advancement of multi-omics technology has sparked interest in exploring cancer stemness from a multi-omics perspective. However, there is a limited number of studies that have attempted to subtype cancer by combining different types of stem cell signatures. METHODS: In this study, 10,323 cancer specimens from 33 TCGA cancer types were clustered based on the enrichment scores of six stemness gene sets, representing two types of stem cell backgrounds: embryonic stem cells (ESCs) and hematopoietic stem cells (HSCs). RESULTS: We identified four subtypes of pan-cancer, termed StC1, StC2, StC3 and StC4, which displayed distinct molecular and clinical features, including stemness, genome integrity, intratumor heterogeneity, methylation levels, tumor microenvironment, tumor progression, responses to chemotherapy and immunotherapy, and survival prognosis. Importantly, this subtyping method for pan-cancer is reproducible at the protein level. CONCLUSION: Our findings indicate that the ESC signature is an adverse prognostic factor in cancer, while the HSC signature and ratio of HSC/ESC signatures are positive prognostic factors. The subtyping of cancer based on ESC and HSC signatures may provide insights into cancer biology and clinical implications of cancer.

Generation of transgene-free hematopoietic stem cells from human induced pluripotent stem cells.

Hematopoietic stem cells (HSCs) are the rare cells responsible for the lifelong curative effects of hematopoietic cell (HC) transplantation. The demand for clinical-grade HSCs has increased significantly in recent decades, leading to major difficulties in treating patients. A promising but not yet achieved goal is the generation of HSCs from pluripotent stem cells. Here, we have obtained vector- and stroma-free transplantable HSCs by differentiating human induced pluripotent stem cells (hiPSCs) using an original one-step culture system. After injection into immunocompromised mice, cells derived from hiPSCs settle in the bone marrow and form a robust multilineage hematopoietic population that can be serially transplanted. Single-cell RNA sequencing shows that this repopulating activity is due to a hematopoietic population that is transcriptionally similar to human embryonic aorta-derived HSCs. Overall, our results demonstrate the generation of HSCs from hiPSCs and will help identify key regulators of HSC production during human ontogeny.