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Ouchi, Y.

Publications and source records attributed to Ouchi, Y..

3 recordsLinked to original sources

From wag to affect: Tail kinematic signatures of canine emotional states in computer-controlled environments

From facial expressions to gestures, animals use multiple signal modalities to express emotions and communicate. In dogs, tail movements are conspicuous behaviours associated with emotional states, but this link remains debated. We investigated canine emotional states underlying tail wagging by systematically analysing differences in tail movements in a computer-controlled task encompassing two non-social Conditions - Rewarded (positive) and Unrewarded (negative), and two Epochs (pre-response and outcome anticipation). Using pose-tracking we found that 11 out of 23 dogs did not wag their tails in at least 75% of trials, suggesting that some dogs may inherently wag less or that tail wagging is primarily a social signal. Our results showed that dogs were more likely to wag during positive anticipation; whereas in the negative condition, despite tail amplitude being more prominent, increased speeds reflected arousal rather than valence. Further work should assess tail kinematics in social contexts to test and extend these findings.

animal behavior and cognition↗

Integrating human iPSC-derived macrophage progenitors into retinal organoids to generate a mature retinal microglial niche

In the retina, microglia are resident immune cells that are essential for retinal development and function. Retinal microglia play a central role in mediating pathological degeneration in diseases such as glaucoma, retinitis pigmentosa, age-related neurodegeneration, ischemic retinopathy and diabetic retinopathy. Current models of mature human retinal organoids (ROs) derived from iPS cell (hiPSC) do not contain resident microglia integrated into retinal layers. Increasing cellular diversity in ROs by including resident microglia would more accurately represent the native retina and better model diseases in which microglia play a key role. In this study, we develop a new 3D in vitro tissue model of microglia-containing retinal organoids by co-culturing ROs and hiPSC-derived macrophage precursor cells (MPCs). We optimized the parameters for successful integration of MPCs into retinal organoids. We then reproducibly integrate MPCs into ROs where they develop into mature microglia (iMG) as seen by 1) migration to the appropriate anatomical locations; 2) development of a mature resting morphology; and 3) expression of mature microglial markers. We show that while in the ROs, MPCs migrate to the equivalent of the outer plexiform layer where retinal microglia cells reside in healthy retinal tissue. While there, they develop a mature morphology characterized by small cell bodies and long branching processes which is only observed in vivo. During this maturation process these microglia cycle through an activated phase followed by a stable mature phase characterized by cell-type specific microglia markers Tmem119 and P2ry12. This co-culture system may be useful for understanding the pathogenesis of retinal diseases involving retinal microglia and for drug discovery.

cell biology↗

Stem cell therapy for skin regeneration using mesenchymal stem cells derived from the progeroid Werner syndrome-specific iPS cells

Adult progeria, Werner syndrome (WS), is an autosomal recessive disorder that develops accelerated aging-associated symptoms after puberty. Refractory skin ulcer of limbs, which is one of the symptoms specific to WS, is seriously painful and sometimes results in amputation. In recent years, cell therapy using mesenchymal stem cells (MSCs) has been attracting attention; however, the effect of WS-derived MSCs on skin ulcers is still unclear. In this study, we generated iPS cells from a patient with WS and a normal subject, differentiated them into MSCs (WS- and NM-iMSC, respectively), and performed cell therapy to a refractory skin ulcer mouse model. As a result, WS-iMSC recapitulated premature senescence phenotypes in vitro. Upon subcutaneous injection around the wounds of mice, WS-iMSC was significantly inferior in wound healing effect compared to NM-iMSC. Proteome and transcriptome analysis revealed altered expression of genes related to angiogenesis, inflammation, and proliferation in WS-iMSC with remarkable downregulation of VEGF, a potent angiogenic factor. In addition, simultaneous administration of recombinant human VEGF and WS-iMSC improved the wound healing effect in vivo. These results indicate that the expression of angiogenic factors is reduced in WS-iMSC, and its supplementation restores the wound healing ability. This finding may pave the way to develop the treatment of intractable skin ulcers of WS.

cell biology↗