Biology subjects

Harada, J.

Publications and source records attributed to Harada, J..

4 recordsLinked to original sources

bioRxiv2026

Protein-independent light harvesting governed by structural heterogeneity

Chlorosomes are the largest known photosynthetic light-harvesting antennas, yet unlike protein-based antennas, they lack protein scaffolds that organize pigment molecules and instead contain self-assembled tubular and lamellar bacteriochlorophyll aggregates. How these antennas achieve directional and efficient energy transfer has remained unresolved. By applying ultrafast transient absorption spectroscopy to individual wild-type and mutant chlorosomes, we resolved six kinetic components obscured by ensemble averaging and assigned each to an excitation process associated with either lamellar or tubular aggregates. Lamellar aggregates tend toward exciton localization and expand light-harvesting capacity, whereas tubular aggregates retain a relatively delocalized excitonic character and serve as the primary energy donors to the baseplate. Structural heterogeneity therefore emerges as a functional feature that balances light-harvesting capacity with robust directional energy transfer. These findings reveal a division of labor among self-assembled pigment aggregates for efficient light harvesting without protein scaffolds.

biophysics↗

bioRxiv2025

Runx/Cbfβ regulates the development of tolerogenic Thetis cells

Establishing immune tolerance to gut microbiota and food antigens upon first exposures during early life is essential to prevent inflammatory bowel diseases and food allergy and depends on induction of peripherally induced Ror{gamma}t expressing regulatory T (Ror{gamma}t+ pTreg) cells1, 2, 3, 4, 5, 6. Recent studies have identified a critical role for Ror{gamma}t expressing antigen-presenting cells (APC), Thetis cells (TCs), in peripheral regulatory T (pTreg) cell differentiation and tolerance to food and commensal microbes7, 8, 9, 10, 11. TCs encompass four distinct subsets, and a subset of TCs, TC IV induces pTreg differentiation, but the transcription factors that control their differentiation are not fully known. Here, using orthogonal genetic approaches to impair Runx/Cbf{beta} activity, we show that development of specific TCs subsets is regulated by Runx/Cbf{beta} transcriptional factor complexes. While attenuated Runx3 by germline mutations resulted in a severe reduction of all Ror{gamma}t+ APCs, mice lacking one of two Cbf{beta} splicing variants, Cbf{beta}2, exhibited a loss of TC II, III and TC IV subsets with associated loss of Ror{gamma}t+ pTreg cells. Conditional inactivation of Runx1 and Runx3 genes by CD11c-Cre led to a specific loss of TC III and TC IV subsets. Strikingly, CD11c-Cre driven transgenic Runx expression, particularly Runx1, led to enhanced TC IV differentiation and thus Ror{gamma}t+ pTreg cells. Furthermore, transgenic Cbf{beta}2 by CD11c-Cre recovered only TC IV subset with restoration of Ror{gamma}t+ pTreg in Cbf{beta}2-deficient mice. Collectively, our findings establish a critical pathway for TC IV differentiation and provide new insights into therapeutic interventions to promote Ror{gamma}t+ pTreg induction in autoimmune and inflammatory diseases.

immunology↗

bioRxiv2024

Tabula Glycine: The whole-soybean single-cell resolution transcriptome atlas

Soybean (Glycine max) is an essential source of protein and oil with high nutritional value for human and animal consumption. To enhance our understanding of soybean biology, it is essential to have accurate information regarding the expression of each of its 55,897 protein-coding genes. Here, we present "Tabula Glycine", the soybean single-cell resolution transcriptome atlas. This atlas is composed of single-nucleus RNA-sequencing data of nearly 120,000 nuclei isolated from 10 different Glycine max organs and morphological structures comprising the entire soybean plant. These nuclei are grouped into 157 different clusters based on their transcriptomic profiles. Among genes, the pattern of activity of transcription factor genes is sufficient to define most cell types and their organ/morphological structure of origin, suggesting that transcription factors are key determinants of cell identity and function. This unprecedented level of resolution makes the Tabula Glycine a unique resource for the plant and soybean communities.

plant biology↗

bioRxiv2020

Branched-Chain Amino Acid Metabolism is Regulated by ERRα and is Further Impaired by Glucose Loading in Type 2 Diabetes

Aims/hypothesisIncreased levels of branched-chain amino acids (BCAAs) are associated with type 2 diabetes pathogenesis. However, most metabolomic studies are limited to an analysis of plasma metabolites under fasting conditions, rather than the dynamic shift in response to a metabolic challenge. Moreover, metabolomic profiles of peripheral tissues involved in glucose homeostasis are scarce and the transcriptomic regulation of genes involved in BCAA catabolism is partially unknown. This study aimed to identify differences in circulating and skeletal muscle BCAA levels in response to an OGTT in individuals with normal glucose tolerance (NGT) or type 2 diabetes. Additionally, transcription factors involved in the regulation of the BCAA gene set were identified. MethodsPlasma and vastus lateralis muscle biopsies were obtained from individuals with NGT or type 2 diabetes before and after an OGTT. Plasma and quadriceps muscles were harvested from skeletal muscle-specific PGC-1 knockout and transgenic mice. BCAA-related metabolites and genes were assessed by LC-MS/MS and RT-PCR, respectively. Small interfering RNA and adenovirus-mediated overexpression techniques were used in primary human skeletal muscle cells to study the role of PGC-1A and ESRRA in the expression of the BCAA gene set. Radiolabeled leucine was used to analyze the impact of ERR knockdown on leucine oxidation. ResultsImpairments in BCAA catabolism in people with type 2 diabetes under fasting conditions were exacerbated after a glucose load. Branched-chain keto acids were reduced 37-56% after an OGTT in the NGT group, whereas no changes were detected in individuals with T2D. These changes were concomitant with a stronger correlation with glucose homeostasis biomarkers and downregulated expression of BCAT2, BCKDH complex subunits and 69% of downstream BCAA-related genes in skeletal muscle. In primary human myotubes overexpressing PGC-1, 61% of the analyzed BCAA genes were upregulated, while 67% were downregulated in the quadriceps of skeletal muscle-specific PGC-1 knockout mice. ESRRA (encoding estrogen-related receptor , ERR) silencing completely abrogated the PGC-1-induced upregulation of BCAA-related genes in primary human myotubes. Conclusions/interpretationMetabolic inflexibility in type 2 diabetes impacts BCAA homeostasis and attenuates the decrease of circulating and skeletal muscle BCAA-related metabolites after a glucose challenge. Transcriptional regulation of BCAA genes in primary human myotubes via a PGC-1 is ERR-dependent. Research in contextO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LICirculating levels of BCAA are elevated in type 2 diabetes. C_LIO_LIPGC-1 is involved in the transcription of the BCAA gene set. C_LI What is the key question?O_LIDoes metabolic inflexibility associated with type 2 diabetes encompass BCAA homeostasis and PGC-1 mediated transcription of the BCAA gene set? C_LI What are the new findings?O_LIBCAA homeostasis is further compromised by a glucose challenge in type 2 diabetes. C_LIO_LIAn OGTT reveals coordinated regulation between BCAA metabolites, blood glucose, and HbA1c levels. C_LIO_LIERR is essential for PGC-1-mediated BCAA gene expression in primary human myotubes. C_LI How might this impact on clinical practice in the foreseeable future?O_LIAn OGTT can be used to underscore impairments in BCAA metabolism. These findings suggest that interventions targeting the PGC-1/ ERR axis may improve BCAA homeostasis. C_LI

physiology↗