Single-Cell RNA Sequencing Unravels Upregulation of Immune Cell Crosstalk in Relapsed Pediatric Ependymoma.

Ependymoma (EPN) is a malignant glial tumor occurring throughout central nervous system, which commonly presents in children. Although recent studies have characterized EPN samples at both the bulk and single-cell level, intratumoral heterogeneity across subclones remains a confounding factor that impedes understanding of EPN biology. In this study, we generated a high-resolution single-cell dataset of pediatric ependymoma with a particular focus on the comparison of subclone differences within tumors and showed upregulation of cilium-associated genes in more highly differentiated subclone populations. As a proxy to traditional pseudotime analysis, we applied a novel trajectory scoring method to reveal cellular compositions associated with poor survival outcomes across primary and relapsed patients. Furthermore, we identified putative cell-cell communication features between relapsed and primary samples and showed upregulation of pathways associated with immune cell crosstalk. Our results revealed both inter- and intratumoral heterogeneity in EPN and provided a framework for studying transcriptomic signatures of individual subclones at single-cell resolution.

Hypothalamic Rax+ tanycytes contribute to tissue repair and tumorigenesis upon oncogene activation in mice.

Hypothalamic tanycytes in median eminence (ME) are emerging as a crucial cell population that regulates endocrine output, energy balance and the diffusion of blood-born molecules. Tanycytes have recently been considered as potential somatic stem cells in the adult mammalian brain, but their regenerative and tumorigenic capacities are largely unknown. Here we found that Rax+ tanycytes in ME of mice are largely quiescent but quickly enter the cell cycle upon neural injury for self-renewal and regeneration. Mechanistically, Igf1r signaling in tanycytes is required for tissue repair under injury conditions. Furthermore, Braf oncogenic activation is sufficient to transform Rax+ tanycytes into actively dividing tumor cells that eventually develop into a papillary craniopharyngioma-like tumor. Together, these findings uncover the regenerative and tumorigenic potential of tanycytes. Our study offers insights into the properties of tanycytes, which may help to manipulate tanycyte biology for regulating hypothalamic function and investigate the pathogenesis of clinically relevant tumors.

The biological basis of sexual orientation: How hormonal, genetic, and environmental factors influence to whom we are sexually attracted.

Humans develop relatively stable attractions to sexual partners during maturation and present a spectrum of sexual orientation from homosexuality to heterosexuality encompassing varying degrees of bisexuality, with some individuals also displaying asexuality. Sexual orientation represents a basic life phenomenon for humans. However, the molecular mechanisms underlying these diverse traits of sexual orientation remain highly controversial. In this review, we systematically discuss recent advancements in sexual orientation research, including those related to measurements and associated brain regions. Current findings regarding sexual orientation modulation by hormonal, genetic, maternal immune system, and environmental factors are summarized in both human and model systems. We also emphasize that future studies should recognize the differences between males and females and pay more attention to minor traits and the epigenetic regulation of sexual orientation. A comprehensive view of sexual orientation may promote our understanding of the biological basis of sex, and that of human reproduction, and evolution.