TIAN, Y. | bioRxiv Science

bioRxiv2024

Orchestrating the Acquisition of Oligodendrocyte Precursor Cell versus Olfactory Bulb Interneuron Fates through Olig1/2 during Mammalian Cortical Gliogenesis and Gliomagenesis

The hijacking of developmental gliogenesis programs is a hallmark of glioblastoma (GBM), in which glial precursor cells (GPCs) typically differentiate into both neurons and glial cells. In GBM, this process is disrupted, leading to the overproduction of proliferative glial-like cells. Our study demonstrates that the knockout of Olig1/2 in both normal development and gliomagenesis causes GPCs to shift from generating highly proliferative oligodendrocyte precursor cells to producing non-proliferative olfactory bulb interneurons. Mechanistically, Olig1/2 play dual roles by orchestrating distinct transcriptional programs in GPCs, particularly inhibiting the expression of Gsx2 through direct binding to its multiple enhancers. Additionally, we provide compelling evidence that human H3.3G34R/V-mutant tumors, a subtype of high-grade gliomas, originate from dorsal cortical-derived GPCs rather than from the previously assumed progenitors in the ventral basal ganglia. Collectively, our findings reveal a previously unrecognized role of Olig1/2 in both gliogenesis and gliomagenesis, offering deeper insights into the connections between normal neural development and tumorigenesis. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=159 HEIGHT=200 SRC="FIGDIR/small/623106v1_ufig1.gif" ALT="Figure 1"> View larger version (69K): org.highwire.dtl.DTLVardef@10ea118org.highwire.dtl.DTLVardef@1725006org.highwire.dtl.DTLVardef@1e3ce25org.highwire.dtl.DTLVardef@f300ee_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

Unraveling the gut microbiota of Tibetan chickens: insights into highland adaptation and ecological advantages

Tibetan animals have several unique advantages owing to the harsh ecological conditions under which they live. Tibetan mammals have been studied extensively. However, understanding of the advantages and underlying mechanisms of the representative high-latitude bird, the Tibetan chicken (Gallus gallus, TC), remains limited. The gut microbiota of animals has been conclusively shown to be closely related to both host health and host environmental adaptation. This study aimed to explore the relationships between the cecal microbiome and the advantages of TCs based on comparisons among three populations: native TCs residing on the plateau, domestic TCs living in the plain, and one native plain species. Metatranscriptomic sequencing revealed a significant enrichment of active Bacteroidetes but a loss of active Firmicutes in native TCs. Additionally, the upregulated expression of genes in the cecal microbiome of native TCs showed enriched pathways related to energy metabolism, glycan metabolism, and the immune response. Furthermore, the expression of genes involved in the biosynthesis of short-chain fatty acids (SCFAs) and secondary bile acids (SBAs) was upregulated in the cecal microbiome of native TCs. Data from targeted metabolomics further confirmed elevated levels of certain SCFAs and SBAs in the cecum of native TCs. Based on the multi-omics association analysis, we proposed that the higher ratio of active Bacteroidetes/Firmicutes may be attributed to the efficient energy metabolism and stronger immunological activity of native TCs. Our findings provide a better understanding of the interactions between gut microbiota and highland adaptation, and novel insights into the mechanisms by which Tibetan chickens adapt to the plateau hypoxic environment. IMPORTANCEThe composition and function of the active cecal microbiome were significantly different between the plateau Tibetan chicken population and the plain chicken population. Higher expression genes related to energy metabolism and immune response were found in the cecal microbiome of the plateau Tibetan chicken population. The cecal microbiome in the plateau Tibetan chicken population exhibited higher biosynthesis of short-chain fatty and secondary bile acids, resulting in higher cecal content of these metabolites. The active Bacteroidetes/Firmicutes ratio in the cecal microbiome may contribute to the high-altitude adaptive advantage of the plateau Tibetan chicken population.

microbiology↗