Southern China is the birthplace of rice-cultivating agriculture and different language families and has also witnessed various human migrations that facilitated cultural diffusions. The fine-scale demographic history in situ that forms present-day local populations, however, remains unclear. To comprehensively cover the genetic diversity in East and Southeast Asia, we generated genome-wide SNP data from 211 present-day Southern Chinese and co-analyzed them with ∼1,200 ancient and modern genomes. In Southern China, language classification is significantly associated with genetic variation but with a different extent of predictability, and there is strong evidence for recent shared genetic history particularly in Hmong–Mien and Austronesian speakers. A geography-related genetic sub-structure that represents the major genetic variation in Southern East Asians is established pre-Holocene and its extremes are represented by Neolithic Fujianese and First Farmers in Mainland Southeast Asia. This sub-structure is largely reduced by admixture in ancient Southern Chinese since > ∼2,000 BP, which forms a “Southern Chinese Cluster” with a high level of genetic homogeneity. Further admixture characterizes the demographic history of the majority of Hmong–Mien speakers and some Kra-Dai speakers in Southwest China happened ∼1,500–1,000 BP, coeval to the reigns of local chiefdoms. In Yellow River Basin, we identify a connection of local populations to genetic sub-structure in Southern China with geographical correspondence appearing > ∼9,000 BP, while the gene flow likely closely related to “Southern Chinese Cluster” since the Longshan period (∼5,000–4,000 BP) forms ancestry profile of Han Chinese Cline.
Multiple myeloma (MM) is a lethal hematological malignancy characterized by abundant myeloid cells in the microenvironment that fuel tumor progression. But the mechanism by which myeloid cells support myeloma cells has not been fully explored. We aimed to examine their effect on bone marrow cells of MM patients by scRNA-seq transcriptome analysis and reveal a high-resolution gene profile of myeloma cells and myeloma-associated myeloid cells. Based on correlation analysis of integrated scRNA-seq and bulk RNA-seq datasets from patients, we confirmed that myeloid-derived S100A9 was involved in TNFSF13B-dependent myeloma cell proliferation and survival. In the animal experiments, S100A9 was found to be critical for MM cell proliferation and survival via TNFSF13B production by myeloid cells, neutrophils, and macrophages. In-vitro analysis of patient primary myeloma cells further demonstrated that enhanced TNFSF13B signaling triggered the canonical NF-κB pathway to boost tumor cell proliferation. All these results suggest that myeloid-derived S100A9 is required for TNFSF13B/TNFRSF13B-dependent cell-fate specification, which provides fresh insights into MM progression.
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