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A single-cell multiomic immune cell atlas from 235 Japanese, including patients with COVID-19 and healthy individuals, linked with host genetics including germline and somatic mutation, plasma proteomics and metagenomics data reveals that immune cells are dynamically regulated in a cell state-dependent manner.

Thymic epithelial cells (TECs) are essential for T cell development but how they develop from progenitors in humans is difficult to study. Here authors set up an in vitro system for thymus organogenesis in which induced pluripotent stem cells give rise to mature and diverse TECs that fully support T cell differentiation.

Through non-cell-autonomous functions, senescent cells can induce secondary senescence in bystander cells. Sogabe et al. generate mouse models of MEK1- or MKK6-induced senescence and use double labeling to map primary and secondary senescence in vivo using single-cell and spatial analysis.

Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.

A genome-wide association study highlights a variant in DOCK2, which is common in East Asian populations but rare in Europeans, as a host genetic risk factor for severe COVID-19.

Analysis of the blood DNA virome in patients with COVID-19 and autoimmune disease associates endogenous HHV-6 (eHHV-6) and high anellovirus load with increased disease risk, most notably for systemic lupus erythematosus. eHHV-6 carriers show a distinct immune response.

By using phylogenetic analyses of multiple microdissected samples from both cancer and non-cancer lesions, unique evolutionary histories of breast cancers harbouring a common driver alteration are shown, providing new insight into how breast cancer evolves.

Photocatalytic water splitting offers a sustainable method for producing green hydrogen but faces challenges due to inefficient materials and systems. Here, the authors report a design for a photocatalytic water-splitting system that efficiently produces hydrogen and oxygen in separate cells.

Using more than 100 independent iPSC lines derived from patients with Alzheimer’s disease, the authors discovered loci associated with the neuronal production of amyloid β and confirmed their influence using RNA interference.

Ryanodine receptor 2 (RyR2) is a Ca²⁺ release channel essential for cardiac excitation-contraction coupling. Here, the authors use structural and functional analysis to reveal RyR2 gating mechanism and its alterations by pathogenic mutations.

Mutations in ryanodine receptor 1 (RyR1), a Ca2+ release channel in skeletal muscle, cause malignant hyperthermia (MH) and are involved in heat stroke. Here, the authors show that an oxolinic acid-derivative RyR1 inhibitor effectively prevents and treats MH and heat stroke in various MH mouse models.

Peripheral blood mononuclear cells from 73 Japanese patients with coronavirus disease 2019 (COVID-19) and 75 healthy controls were analyzed using single-cell transcriptomics. Combining these data with genotyping data highlights the interplay between host genetics and the immune response in modulating disease severity.

Development of an optical method to inactivate synaptic receptors in mice with temporal precision will enable a better understanding of their roles in cognition.

Authentic hypoblast cells created from naive human pluripotent stem cells (hPSCs) spontaneously assemble with naive hPSCs to form a three-dimensional bilaminar structure (bilaminoids) with a pro-amniotic-like cavity.

De novo DNA methylation is carried out by DNMT3A and DNMT3B, but the distinct functions of these two enzymes is poorly understood. Here the authors present a comprehensive, genome-wide identification of target sites for de novo DNA methylation by the DNMT3A and DNMT3B in mouse ES cells and embryos, identifying unique de novo DNA methylation target sites for both DNMT3 enzymes.

It is difficult to construct hydrogels with high stiffness at ultralow solid content. Here, low-molecular-weight cellulose was synthesized in the presence of cellulose-binding polysaccharides to construct stiff hydrogels that exhibit Young’s modulus of 386 kPa at a low solid content of 1.34% (w/v).

The dorsal raphe nucleus (DRN) is known to modulate aggressive behaviour in rodents. Here the authors show that glutamatergic projections from the lateral habenula to DRN modulate aggression between male mice.

A system involving in vitro induction of presomitic mesoderm recapitulates oscillatory expression of core segmentation clock genes and travelling-wave-like gene expression, suggesting that this system can be used to study the human segmentation clock and provide insights into diseases associated with human axial skeletogenesis.

Higher-order chromatin organization regulates the expression of transcriptional programs that control cell function. Here, the authors show that chromatin interaction profiles and nuclear positions at developmental gene loci differ between human somatic and pluripotent stem cells.

Cellular reprogramming and cancer development share properties. Here, the authors examine the impact of in vivo reprogramming on Kras-induced cancer and show reprogramming-mediated repression of somatic cell enhancers in conjunction with Kras mutation results in rapid PDAC development.

Lentinan (Len) is a linear (1,3)-β-d-glucan with two of its five main-chain glucose-bearing (1,6)-β-d-glucan side chains and has been clinically used for cancer treatment in combination with chemotherapy. In this paper, a structural analysis of Len was conducted using SAXS, GPC, and ¹³C quantitative NMR techniques, and a comparative study with other β-glucans was performed. The complexation between dA₄₀ and Len caused the hypochromic effect. Len and dA₄₀ showed a similar complexation with that of SPG; two main chain glucoses bind to one dA moiety by GPC.

The mechanisms by which in vivo expression of the Yamanaka transcription factors (OSKM) renders somatic cells permissive for differentiation remain unclear. Here, the authors show that in vivo reprogramming using OSKM generates germ cell tumors and drives acquisition of totipotency-like features in somatic cells through DMRT1.

The EWS-ATF1 fusion gene causes clear cell sarcoma (CCS). Here, the authors show that the downstream effects of EWS-ATF1 expression are strictly context dependent, and reveal the cell of origin for CCS to be Tppp3-expressing cells in peripheral nerves.

The transcription factor Srf is a central regulator of immediate-early and actin cytoskeletal genes. Here the authors show that Srf is activated by repression of β-actin, promoting iPSC reprogramming of neural progenitor cells and hepatoblasts by repressing cell-type specific genes.

Derivation of female mouse embryonic stem cells under certain conditions induces a loss of DNA methylation and erasure of genomic imprints, which are not recovered and that may contribute to observed impaired development.

DNA origami-based integrated gene transcription modules enable the rational design of transcription activity. Architectural modalities between gene and RNA polymerase allow the autonomous response to various signals with reprogrammable logic gates.

We investigated the crystallization behavior and crystal orientation of poly(ɛ-caprolactone) (PCL) blocks confined in the polyethylene (PE) lamellar morphology of PCL-block-PE (PCL-b-PE) with different PE crystallinities χ_PE and PCL layer thicknesses d_PCL. We found that the crystallization behavior of PCL blocks in PCL-b-PE with higher χ_PE and smaller d_PCL was different from that in other PCL-b-PE copolymers. In addition, the orientation of PCL crystals significantly changed with changing crystallization temperature in PCL-b-PE with higher χ_PE and smaller d_PCL, whereas it did not change in PCL-b-PE with lower χ_PE or larger d_PCL.

The melting temperature of poly(ɛ-caprolactone) blocks, T_m,PCL, in poly(ɛ-caprolactone)-block-polyethylene is investigated as a function of the volume fraction of poly(ɛ-caprolactone) blocks in the system, φ_PCL, and compared with that in poly(ɛ-caprolactone)-block-polybutadiene, the precursor of poly(ɛ-caprolactone)-block-polyethylene with an identical poly(ɛ-caprolactone) molecular weight. T_m,PCL for poly(ɛ-caprolactone)-block-polyethylene is always higher than that for poly(ɛ-caprolactone)-block-polybutadiene, and the difference in T_m,PCL increases steadily with increasing φ_PCL.

Delineation of the zone-specific dynamics of hepatocytes during pregnancy in mice demonstrates that midgestational periportal hepatocyte proliferation is critical for maternal glucose homeostasis during late pregnancy.

Naked mole rats are found to be resistant to cancer development through dampened inflammatory response due to genetically determined impaired necroptosis, with essential necroptosis genes RIPK3 and MLKL containing mutations causing premature stop codons.