We present a resolved star spectroscopic survey of 15 dwarf spheroidal (dSph) satellites of the Andromeda galaxy (M31). We filter foreground contamination from Milky Way (MW) stars, noting that MW substructure is evident in this contaminant sample. We also filter M31 halo field giant stars and identify the remainder as probable dSph members. We then use these members to determine the kinematical properties of the dSphs. For the first time, we confirm that And XVIII, XXI, and XXII show kinematics consistent with bound, dark-matter-dominated galaxies. From the velocity dispersions for the full sample of dSphs we determine masses, which we combine with the size and luminosity of the galaxies to produce mass-size-luminosity scaling relations. With these scalings we determine that the M31 dSphs are fully consistent with the MW dSphs, suggesting that the well-studied MW satellite population provides a fair sample for broader conclusions. We also estimate dark matter halo masses of the satellites and find that there is no sign that the luminosity of these galaxies depends on their dark halo mass, a result consistent with what is seen for MW dwarfs. Two of the M31 dSphs (And XV, XVI) have estimated maximum circular velocities smaller than 12 km s −1 (to 1σ ), which likely places them within the lowest-mass dark matter halos known to host stars (along with Boötes I of the MW). Finally, we use the systemic velocities of the M31 satellites to estimate the mass of the M31 halo, obtaining a virial mass consistent with previous results.

Emerging evidence suggests that cancer is populated and maintained by tumor initiating cells (TICs) with stem-like properties similar to that of adult tissue stem cells. Despite recent advances, the molecular regulatory mechanisms that may be shared between normal and malignant stem cells remain poorly understood. Here we show that the ΔNp63 isoform of the Trp63 transcription factor promotes normal mammary stem cell (MaSC) activity by increasing the expression of the Wnt receptor Fzd7, thereby enhancing Wnt signaling. Importantly, Fzd7-dependent enhancement of Wnt signaling by ΔNp63 also governs tumor initiating activity of the basal subtype of breast cancer. These findings establish ΔNp63 as a key regulator of stem cells in both normal and malignant mammary tissues and provide direct evidence that breast cancer TICs and normal MaSCs share common regulatory mechanisms.

The stem cell niche is a specialized environment that dictates stem cell function during development and homeostasis. We show that Dll1, a Notch pathway ligand, is enriched in mammary gland stem cells (MaSCs) and mediates critical interactions with stromal macrophages in the surrounding niche in mouse models. Conditional deletion of Dll1 reduced the number of MaSCs and impaired ductal morphogenesis in the mammary gland. Moreover, MaSC-expressed Dll1 activates Notch signaling in stromal macrophages, increasing their expression of Wnt family ligands such as Wnt3, Wnt10A, and Wnt16, thereby initiating a feedback loop that promotes the function of Dll1-expressing MaSCs. Together, these findings reveal functionally important cross-talk between MaSCs and their macrophageal niche through Dll1-mediated Notch signaling.

Meningiomas arising from the meningothelial central nervous system lining are the most common primary intracranial tumors, and a significant cause of neurologic morbidity and mortality 1 . There are no effective medical therapies for meningioma patients 2,3 , and new treatments have been encumbered by limited understanding of meningioma biology. DNA methylation profiling provides robust classification of central nervous system tumors 4 , and can elucidate targets for molecular therapy 5 . Here we use DNA methylation profiling on 565 meningiomas integrated with genetic, transcriptomic, biochemical, and single-cell approaches to show meningiomas are comprised of 3 epigenetic groups with distinct clinical outcomes and biological features informing new treatments for meningioma patients. Merlin-intact meningiomas (group A, 34%) have the best outcomes and are distinguished by a novel apoptotic tumor suppressor function of NF2/Merlin. Immune-enriched meningiomas (group B, 38%) have intermediate outcomes and are distinguished by immune cell infiltration, HLA expression, and lymphatic vessels. Hypermitotic meningiomas (group C, 28%) have the worst outcomes and are distinguished by convergent genetic mechanisms misactivating the cell cycle. Consistently, we find cell cycle inhibitors block meningioma growth in cell culture, organoids, xenografts, and patients. Our results establish a framework for understanding meningioma biology, and provide preclinical rationale for new therapies to treat meningioma patients.