Biology subjects

Moriguchi, T.

Publications and source records attributed to Moriguchi, T..

4 recordsLinked to original sources

bioRxiv2026

Co-targeting an AMPK--MAPK axis reprograms CAFs and suppresses PDAC

Pancreatic ductal adenocarcinoma (PDAC) is a fatal cancer characterized by limited therapeutic options and a highly treatment-resistant tumor microenvironment. Beyond tumor-intrinsic genetic alterations, growing evidence indicates that host-microbiome interactions influence cancer progression through microbial metabolites. However, how microbiome-derived metabolites influence oncogenic signaling in PDAC remains unclear. Here, integrated profiling revealed a consistent reduction of the microbial metabolite acetic acid in fecal samples from treatment-naive patients with PDAC and in a genetically defined Drosophila model recapitulating key PDAC driver alterations. Acetic acid activates AMP-activated protein kinase, and pharmacological activation of this pathway together with inhibition of mitogen-activated protein kinase signaling suppressed tumor growth in fly and mouse models. Combined pathway targeting restored AMPK activity and suppressed cancer-associated fibroblast activation. These findings identify a microbiome-associated metabolic vulnerability in PDAC and suggest that coordinated targeting of metabolic and oncogenic signaling may restrain tumor progression and improve therapeutic strategies.

cancer biology↗

bioRxiv2025

Maternal care during early development is necessary for the acquisition of a calming response to back stroking

In many mammals, early postnatal interactions between caregivers and offspring involve rich physical contact, including stroking, holding, and grooming. Offspring typically remain calm and close to the caregiver during such stimulation. Although these behaviors are thought to support emotional regulation and bonding during infancy, the underlying mechanisms and the role of prior experience remain unclear. Here, we demonstrate that back stroking induces a conserved calming response in both human infants and mouse pups, characterized by reduced movement and heart rate. In mouse pups, stroking further facilitated sleep onset, increased EEG delta power, and attenuated stress-induced corticosterone elevations. These sleep-promoting and stress-buffering effects were absent in artificially reared pups deprived of postnatal maternal contact, underscoring the importance of early tactile experience. Transcriptomic analysis revealed downregulation of the voltage-gated calcium channel subunit gene Cacna1b in the hypothalamus of artificially reared pups. Moreover, knockdown of hypothalamic Cacna1b in maternally reared pups abolished stroking-induced calming and sleep-promoting effects. This study identifies a conserved, experience-dependent calming response to affiliative tactile input, biologically embedded through plasticity, that supports physiological regulation and stress resilience during early development. Our results highlight that affiliative tactile sensation, like discriminative tactile sensation, depends on early experience to organize neural mechanisms regulating internal states. SignificanceEarly-life physical contact with caregivers is essential for healthy emotional and physiological development in mammals, but its underlying mechanisms remain unclear. We show that back stroking induces a conserved calming response in both human infants and mouse pups, reducing movement, heart rate, and promoting sleep. These effects depend on early tactile experience and are mediated by Cacna1b expression in the hypothalamus. Our findings identify a plastic, experience-dependent pathway through which affiliative tactile input modulates internal states, revealing how parental care supports stress resilience and sleep physiology during early development.

neuroscience↗

bioRxiv2025

The sympathoadrenal contribution to inferior vena cava formation

Vascular development is fundamental during embryogenesis. Although the molecular and cellular mechanisms of vascular formation have been extensively studied, the developmental basis common to anatomical variations in major veins remains poorly understood1-4. In particular, the renal segment of the inferior vena cava (IVC) exhibits marked anatomical variability, and these structural differences often affect the safety of retroperitoneal surgeries5,6. Here we show that the renal segment of the IVC in mouse embryos does not arise from the subcardinal vein (SubCV), as classically proposed7, but instead forms from a vascular plexus in the para-aortic ridge (PAR) closely associated with developing sympathetic and adrenal tissues. Three-dimensional imaging with molecular markers revealed the vascular plexus in PAR arises independently of the SubCV and develops in Zuckerkandl organ and adrenal gland primordia. Moreover, genetic models demonstrated that the development of the sympathetic and adrenal tissues contributes to the organization and remodeling of this vascular network. This sympathoadrenal contribution contrasts with the classical mesonephros-centric model and explains the consistent IVC structures observed even in the absence of renal development. Our findings suggest a mammal-specific mode of IVC formation driven by the emergence of dominant sympathetic paraganglia and reduced reliance on mesonephric filtration. This revised developmental framework provides insight into the evolutionary divergence of venous anatomy and may help interpret clinically significant vascular variations during abdominal surgery.

developmental biology↗

bioRxiv2021

The epigenetic eraser LSD1 lies at the apex of a reversible erythroid to myeloid cell fate decision

H3K4Me demethylase KDM1a/LSD1 is a therapeutic target for multiple diseases, including the {beta}-globinopathies (sickle cell disease and {beta}-thalassemia) since its inactivation has been shown to lead to robust induction of the fetal globin genes. Here we examined the consequences of conditional inactivation of Lsd1 in adult red blood cells using a new Gata1creERT2 BAC transgene. Loss of Lsd1 activity in mice blocked erythroid differentiation and expanded GMP-like cells, converting hematopoietic differentiation potential from an erythroid to a myeloid fate. The analogous phenotype was also observed in human HSPC, coincident with induction of myeloid transcription factors (e.g. PU.1 and CEBP). Finally, blocking the activity of myeloid transcription factors PU.1 or RUNX1 at the same time as LSD1 reverted myeloid lineage conversion to an erythroid phenotype. The data show that LSD1 promotes erythropoiesis by repressing myeloid cell fate, and that inhibition of myeloid differentiation reverses the lineage switch caused by LSD1 inactivation.

developmental biology↗