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Nature Papers Examine Gene Expression Across Land Plants, Tumor Cell Response to Natural Killer Cells

A comparative analysis of gene expression in the organs and gametes of land plants is published in Nature Plants this week, providing new insights into the mechanisms underlying organogenesis and reproduction in them. Land plants date back to around 470 million years ago and the appearance of plant organs mediated their explosive radiation, shaping the Earth's biosphere and enabling the establishment of terrestrial animal life. Yet, no comprehensive comparisons of organ- and tissue-specific transcriptomes in land plants have been done. To address this, a team led by scientists from Nanyang Technological University in China generated gene expression atlases for 10 land plants comprising bryophytes, vascular plants, gymnosperms, and flowering plants. By analyzing and comparing the atlases, the investigators found hundreds of organ- and gamete-specific orthogroups and discovered that the transcriptomes of most organs are conserved across land plants. Other findings include numerous transcription factors and kinases that are potentially important for pollen biogenesis and function.

A study examining the mechanism that controls how tumor cells respond to natural killer (NK) cells is presented in Nature Genetics this week, uncovering new details about NK/tumor cell interactions that may help in the development of personalized cancer therapies. Recent studies suggest that infusions of allogenic NK cells can be safely performed across human leukocyte antigen barriers and avoid the graft-versus-host reactions that limit immunotherapies based on administration of allogeneic T cells. Amid growing interest in the anticancer potential of NK cells, a group led by researchers from the Dana-Farber Cancer Institute aimed to identify the molecular features in human tumor cells that determine their degree of sensitivity to human allogeneic NK cells, and to confirm whether these mechanisms are broadly generalizable to genotypically diverse types of tumors. To do so, they used a technology dubbed profiling relative inhibition simultaneously in mixtures, or PRISM, to simultaneously examine the NK cell responsiveness of several hundreds of molecularly annotated DNA-barcoded solid tumor cell lines in a multiplexed format. They also used CRISPR-based gene editing to examine at genome scale which genes regulate the response versus resistance of several solid tumor cell lines to NK cells. From this, they found that NK cell-sensitive tumor cells tend to exhibit mesenchymal-like transcriptional programs; high transcriptional signatures for chromatin remodeling complexes; high levels of B7-H6, an activating ligand for an NK receptor; and low levels of HLA-E/antigen presentation genes. Notably, the transcriptional signatures of NK cell-sensitive tumor cells correlate with resistance to immune check point inhibitors, suggesting that cells resistant to other forms of immunotherapy may still be vulnerable to NK cells.

The Scan

Positive Framing of Genetic Studies Can Spark Mistrust Among Underrepresented Groups

Researchers in Human Genetics and Genomics Advances report that how researchers describe genomic studies may alienate potential participants.

Small Study of Gene Editing to Treat Sickle Cell Disease

In a Novartis-sponsored study in the New England Journal of Medicine, researchers found that a CRISPR-Cas9-based treatment targeting promoters of genes encoding fetal hemoglobin could reduce disease symptoms.

Gut Microbiome Changes Appear in Infants Before They Develop Eczema, Study Finds

Researchers report in mSystems that infants experienced an enrichment in Clostridium sensu stricto 1 and Finegoldia and a depletion of Bacteroides before developing eczema.

Acute Myeloid Leukemia Treatment Specificity Enhanced With Stem Cell Editing

A study in Nature suggests epitope editing in donor stem cells prior to bone marrow transplants can stave off toxicity when targeting acute myeloid leukemia with immunotherapy.