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PNAS Studies on Supercentenarians, Blood Cell Differentiation in AML, Beetle Evolution

Editor's Note: Some of the articles described below are not yet available at the PNAS site, but they are scheduled to be posted some time this week.

Researchers from the Riken Center for Integrative Medical Sciences and the Keio University School of Medicine describe a cytotoxic CD4 T cell immune signature in blood samples from supercentenarians — individuals who are at least 110 years old. Using single-cell RNA sequencing, the team took a look at transcriptomic patterns in circulating immune cells from seven supercentenarians and five controls under 110, focusing on more than 61,200 individual peripheral blood mononuclear cells. Along with enhanced representation of CD4 cytotoxic T lymphocytes, particularly those with expression features resembling CD8 cytotoxic T lymphocytes, the authors saw expansion of specific CD4 T cell clones in the supercentenarians, based on subsequent single-cell T cell receptor sequencing on two individuals reaching an exceptional age. "[G]enerally CD4 T cells have helper, but not cytotoxic, functions under physiological conditions," they explain, noting that the "conversion of helper CD4 T cells to a cytotoxic variety might be an adaptation to the late stage of aging." GenomeWeb has more on this, here.

For another paper set to come out in PNAS this week, a team from Oregon Health and Science University, Microsoft Research, and the University of Washington provides evidence suggesting relatively subtle changes in the proportion of hematopoietic stem cells that differentiate into mature blood cells can prompt acute myeloid leukemia (AML)-related hematopoietic blast cells to build up in the blood and bone marrow. The researchers did differentiation rate modeling, fluorescent in situ hybridization, and cell sequencing, uncovering mature blood cell types that continued to arise through differentiation in AML, albeit at lower-than-usual rates. "We experimentally validated that mature myeloid cells have the same genotype as leukemic blasts, demonstrating that there is not a complete block in differentiation," the authors report, noting that the results may impact if, and how, treatments targeting differentiation may be used in AML in the future. 

An international team led by investigators in the US and Germany takes a look at the evolutionary history of beetles in the Coleoptera order, focusing on dramatic diversification within the lineage and the evolution of specialized plant-feeding lifestyles. In addition to a phylogenetic analysis built on more than 4,800 nuclear genes from 146 species of beetles or related insects, the researchers delved into specific features of beetle diversification with a broader analysis of 521 species represented by a few dozen genes, together with additional genome or transcriptome sequences. The analyses hinted that many beetles may have co-evolved and diversified with flowering plants, for example, nabbing enzyme-coding genes that help break down plant cell walls through horizontal gene transfer from bacteria and fungi. "Our findings clarify beetle phylogenetic relationships and reveal new insights into the evolution of specialized herbivory and why there are so many species of beetles," they report.