Taxonomic and functional restoration of tallgrass prairie soil microbial communities in comparison to remnant and agricultural soils.

Restoring ecosystems requires the re-establishment of diverse soil microbial communities that drive critical ecosystem functions. In grasslands, restoration and management require the application of disturbances like fire and grazing. Disturbances can shape microbial taxonomic composition and potentially functional composition as well.

Detection and targeting of splicing deregulation in pediatric acute myeloid leukemia stem cells.

Pediatric acute myeloid leukemia (pAML) is typified by high relapse rates and a relative paucity of somatic DNA mutations. Although seminal studies show that splicing factor mutations and mis-splicing fuel therapy-resistant leukemia stem cell (LSC) generation in adults, splicing deregulation has not been extensively studied in pAML. Herein, we describe single-cell proteogenomics analyses, transcriptome-wide analyses of FACS-purified hematopoietic stem and progenitor cells followed by differential splicing analyses, dual-fluorescence lentiviral splicing reporter assays, and the potential of a selective splicing modulator, Rebecsinib, in pAML.

Reversal of malignant ADAR1 splice isoform switching with Rebecsinib.

Adenosine deaminase acting on RNA1 (ADAR1) preserves genomic integrity by preventing retroviral integration and retrotransposition during stress responses. However, inflammatory-microenvironment-induced ADAR1p110 to p150 splice isoform switching drives cancer stem cell (CSC) generation and therapeutic resistance in 20 malignancies. Previously, predicting and preventing ADAR1p150-mediated malignant RNA editing represented a significant challenge.

Gut Metabolites Are More Predictive of Disease and Cohoused States than Gut Bacterial Features in a Polycystic Ovary Syndrome-Like Mouse Model.

Polycystic ovary syndrome (PCOS) impacts ∼10% of reproductive-aged women worldwide. In addition to infertility, women with PCOS suffer from metabolic dysregulation which increases their risk of developing type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease. Studies have shown differences in the gut microbiome of women with PCOS compared to controls, a pattern replicated in PCOS-like mouse models.

ADAR1 Activation Drives Leukemia Stem Cell Self-Renewal by Impairing Let-7 Biogenesis.

Post-transcriptional adenosine-to-inosine RNA editing mediated by adenosine deaminase acting on RNA1 (ADAR1) promotes cancer progression and therapeutic resistance. However, ADAR1 editase-dependent mechanisms governing leukemia stem cell (LSC) generation have not been elucidated. In blast crisis chronic myeloid leukemia (BC CML), we show that increased JAK2 signaling and BCR-ABL1 amplification activate ADAR1.

Reversion to an embryonic alternative splicing program enhances leukemia stem cell self-renewal.

Formative research suggests that a human embryonic stem cell-specific alternative splicing gene regulatory network, which is repressed by Muscleblind-like (MBNL) RNA binding proteins, is involved in cell reprogramming. In this study, RNA sequencing, splice isoform-specific quantitative RT-PCR, lentiviral transduction, and in vivo humanized mouse model studies demonstrated that malignant reprogramming of progenitors into self-renewing blast crisis chronic myeloid leukemia stem cells (BC LSCs) was partially driven by decreased MBNL3. Lentiviral knockdown of MBNL3 resulted in reversion to an embryonic alternative splice isoform program typified by overexpression of CD44 transcript variant 3, containing variant exons 8-10, and BC LSC proliferation.