Metabolism-based targeting of MYC via MPC-SOD2 axis-mediated oxidation promotes cellular differentiation in group 3 medulloblastoma.

Group 3 medulloblastoma (G3 MB) carries the worst prognosis of all MB subgroups. MYC oncoprotein is elevated in G3 MB tumors; however, the mechanisms that support MYC abundance remain unclear. Using metabolic and mechanistic profiling, we pinpoint a role for mitochondrial metabolism in regulating MYC.

An OTX2-PAX3 signaling axis regulates Group 3 medulloblastoma cell fate.

OTX2 is a potent oncogene that promotes tumor growth in Group 3 medulloblastoma. However, the mechanisms by which OTX2 represses neural differentiation are not well characterized. Here, we perform extensive multiomic analyses to identify an OTX2 regulatory network that controls Group 3 medulloblastoma cell fate.

CD271 Cells Are Diagnostic and Prognostic and Exhibit Elevated MAPK Activity in SHH Medulloblastoma.

The extensive heterogeneity both between and within the medulloblastoma subgroups underscores a critical need for variant-specific biomarkers and therapeutic strategies. We previously identified a role for the CD271/p75 neurotrophin receptor (p75NTR) in regulating stem/progenitor cells in the SHH medulloblastoma subgroup. Here, we demonstrate the utility of CD271 as a novel diagnostic and prognostic marker for SHH medulloblastoma using IHC analysis and transcriptome data across 763 primary tumors.

Differential placental hormone gene expression during pregnancy in a transgenic mouse containing the human growth hormone/chorionic somatomammotropin locus.

The human (h) growth hormone/chorionic somatomammotropin (GH/CS) gene locus presents a unique model to gain insight into the molecular mechanisms that have allowed a closely related family of genes to be expressed in two distinct cell lineages/tissues: pituitary somatotrophs and placental syncytiotrophoblasts. However, studies of external factors that regulate gene expression have been somewhat limited by (i) a lack of human cell lines expressing endogenous GH or CS appropriately; and (ii) the fact that the GH/CS locus is unique to primates and thus does not exist in rodents. In the current study, a transgenic (171 h GH/CS-TG) mouse was generated containing the intact hGH/CS gene cluster and hGH locus control region (LCR) in a 171-kilobase DNA fragment.

FGF-16 is required for embryonic heart development.

Fibroblast growth factor 16 (FGF-16) expression has previously been detected in mouse heart at mid-gestation in the endocardium and epicardium, suggesting a role in embryonic heart development. More specifically, exogenously applied FGF-16 has been shown to stimulate growth of embryonic myocardial cells in tissue explants. We have generated mice lacking FGF-16 by targeting the Fgf16 locus on the X chromosome.