Re-programing Chromatin with a Bifunctional LSD1/HDAC Inhibitor Induces Therapeutic Differentiation in DIPG

Cancer Cell, Год журнала: 2019, Номер 36(5), С. 528 - 544.e10

Опубликована: Окт. 17, 2019

Язык: Английский

---

Histone Variant and Cell Context Determine H3K27M Reprogramming of the Enhancer Landscape and Oncogenic State

Molecular Cell, Год журнала: 2019, Номер 76(6), С. 965 - 980.e12

Опубликована: Окт. 3, 2019

Язык: Английский

---

The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location

Nature Genetics, Год журнала: 2022, Номер 54(12), С. 1881 - 1894

Опубликована: Дек. 1, 2022

Abstract Histone 3 lysine27-to-methionine (H3-K27M) mutations most frequently occur in diffuse midline gliomas (DMGs) of the childhood pons but are also increasingly recognized adults. Their potential heterogeneity at different ages and locations is vastly understudied. Here, through dissecting single-cell transcriptomic, epigenomic spatial architectures a comprehensive cohort patient H3-K27M DMGs, we delineate how age anatomical location shape glioma cell-intrinsic -extrinsic features light shared driver mutation. We show that stem-like oligodendroglial precursor-like cells, present across all clinico-anatomical groups, display varying levels maturation dependent on location. reveal previously underappreciated relationship between mesenchymal cancer cell states age, linked to age-dependent differences immune microenvironment. Further, resolve organization DMG populations identify mitotic oligodendroglial-lineage niche. Collectively, our study provides powerful framework for rational modeling therapeutic interventions.

Язык: Английский

---

Mechanisms of Polycomb group protein function in cancer

Cell Research, Год журнала: 2022, Номер 32(3), С. 231 - 253

Опубликована: Янв. 19, 2022

Cancer arises from a multitude of disorders resulting in loss differentiation and stem cell-like phenotype characterized by uncontrolled growth. Polycomb Group (PcG) proteins are members multiprotein complexes that highly conserved throughout evolution. Historically, they have been described as essential for maintaining epigenetic cellular memory locking homeotic genes transcriptionally repressed state. What was initially thought to be function restricted few target genes, subsequently turned out much broader relevance, since the main role PcG is ensure dynamically choregraphed spatio-temporal regulation their numerous during development. Their ability modify chromatin landscapes refine expression master controlling major switches decisions under physiological conditions often misregulated tumors. Surprisingly, functional implication initiation progression cancer may either dependent on complexes, or specific subunit acts independently other members. In this review, we describe how play pleiotropic altering broad spectrum biological processes such proliferation-differentiation balance, metabolism immune response, all which crucial tumor progression. We also illustrate interfering with functions can provide powerful strategy counter

Язык: Английский

---

K27M in canonical and noncanonical H3 variants occurs in distinct oligodendroglial cell lineages in brain midline gliomas

Nature Genetics, Год журнала: 2022, Номер 54(12), С. 1865 - 1880

Опубликована: Дек. 1, 2022

Язык: Английский

---