Cell Competition Eliminates Aneuploid Human Pluripotent Stem Cells.

Human pluripotent stem cells (hPSCs) maintain diploid populations for generations despite a persistently high rate of mitotic errors that cause aneuploidy, or chromosome imbalances. Consequently, to maintain genome stability, aneuploidy must inhibit hPSC proliferation, but the mechanisms are unknown. Here, we surprisingly find that homogeneous aneuploid populations of hPSCs proliferate unlike aneuploid non-transformed somatic cells.

STAG2 mutations regulate 3D genome organization, chromatin loops, and Polycomb signaling in glioblastoma multiforme.

Inactivating mutations of genes encoding the cohesin complex are common in a wide range of human cancers. STAG2 is the most commonly mutated subunit. Here we report the impact of stable correction of endogenous, naturally occurring STAG2 mutations on gene expression, 3D genome organization, chromatin loops, and Polycomb signaling in glioblastoma multiforme (GBM).

A pluripotent developmental state confers a low fidelity of chromosome segregation.

During in vitro propagation, human pluripotent stem cells (hPSCs) frequently become aneuploid with incorrect chromosome numbers due to mitotic chromosome segregation errors. Yet, it is not understood why hPSCs exhibit a low mitotic fidelity. Here, we investigate the mechanisms responsible for mitotic errors in hPSCs and show that the primary cause is lagging chromosomes in anaphase with improper merotelic microtubule attachments.

Myomegalin regulates Hedgehog pathway by controlling PDE4D at the centrosome.

Mutations in the hedgehog (Hh) signaling are implicated in birth defects and cancers, including medulloblastoma (MB), one of the most malignant pediatric brain tumors. Current Hh inhibitors face the challenge of drug resistance and tumor relapse, urging new insights in the Hh pathway regulation. Our previous study revealed how PDE4D controls global levels of cAMP in the cytoplasm to positively regulate Hh signaling; in the present study, we found that a specific isoform PDE4D3 is tethered to the centrosome by Myomegalin (Mmg), a centrosome/Golgi-associated protein.

A novel MYOC heterozygous mutation identified in a Chinese Uygur pedigree with primary open-angle glaucoma.

Purpose: To characterize the clinical features of a Chinese Uygur pedigree with primary open-angle glaucoma (POAG) and to identify mutations in two candidate genes, trabecular meshwork inducible glucocorticoid response (MYOC/TIGR) and human dioxin-inducible cytochrome P450 (CYP1B1).

Methods: Twenty one members from a Chinese Uygur family of four generations were included in the study. All participants underwent complete ophthalmologic examinations.