Biology subjects

Kanaya, M.

Publications and source records attributed to Kanaya, M..

3 recordsLinked to original sources

bioRxiv2025

Visualization of the microstructure and distribution of follicles in deep human ovaries using speckle-modulated optical coherence microscopy

Ovarian tissue cryopreservation (OTC) and transplantation (OTT) are the only fertility preservation (FP) options for children, adolescents, and young adults (CAYA) who dont enough time until treatment of primary disease. OTC is still unestablished FP options, but it is expected that selective preservation of ovarian tissue with high follicle density will enhance pregnancy efficiency. Despite its value as a noninvasive follicle visualization method, optical coherence microscopy (OCM) lacks sufficient spatial resolution, imaging depth, and noise suppression capabilities to resolve fine follicular structures in deep ovarian tissue. In this study, we applied speckle modulation to a wavelength-swept OCM optical system in the near-infrared region to visualize the fine structure of follicles distributed in deep tissues. OCM images of 4-day-old mice revealed dense superficial-layer distributions of primordial follicles. These follicles were distinguishable from primary follicles, which were surrounded by a single layer of granulosa cells. In 14-day-old ovarian tissue, secondary follicles exhibited spatial dominance, and the fine structures constituting the follicles were successfully visualized. In ovarian tissues extracted from a patient diagnosed with acute myeloid leukemia (AML), the fine structures of primordial follicles were visualized to a depth of 300 m, and a comparison with HE staining revealed that follicle density varied significantly depending on the ovarian regions. Speckle modulation-assisted OCM visualized the microstructure of follicles with varying degrees of maturation in human ovaries at the depth necessary for clinical application. Overall, this technology enables quantitative ovarian reserve assessment and selective cryopreservation of ovarian tissue rich in immature follicles, supporting FP in CAYA diagnosed with cancer.

bioengineering↗

bioRxiv2025

Toggling of NKG2A expression drives functional specialization of iPSC-derived CAR NK cells

Induced pluripotent stem cell (iPSC)-derived natural killer (iNK) cells offer a promising platform for off-the-shelf immunotherapy against hematological malignancies. NK cell function is dynamically regulated through education driven by inhibitory receptors, including CD94/NKG2A and killer cell immunoglobulin-like receptors (KIR). However, the acquisition of inhibitory receptors in iNK cells and their role during differentiation and education remains poorly defined. In this study, we monitored receptor repertoires, transcriptional states, and functional responses in a range of genetically engineered iNK cell lines. Transcriptional reference mapping placed iNK cells close to cytokine-activated NKG2A+ CD56dim peripheral blood (PB) NK cells. Despite their early differentiation stage, iNK cells displayed a well-developed cytotoxic effector program, which was also reflected in high protein expression of Eomes, granzyme B, and activating receptors DNAM-1 and NKG2D. Acquisition of NKG2A by iNK cells was associated with a more differentiated transcriptional state and superior functional responses against a broad range of targets, including those expressing low to moderate levels of HLA-E, suggesting attenuated inhibitory signaling through NKG2A in iNKs. CRISPR knockout of {beta}2-microglobulin (B2) in iNK cells revealed that the functional potency of NKG2A+ iNK cells was independent of educating interactions with HLA-E in cis or trans. Finally, CRISPR-mediated ablation of NKG2A led to a spontaneous compensatory surface expression of CD94/NKG2C heterodimers, associated with enhanced IFN-{gamma} production and cytotoxic activity against target cells with forced high expression of single-chain {beta}2m-HLA-E-peptide trimers. Our results indicate an education-independent functional maturation of iNK cells, characterized by potent effector programs coupled with a favorable early-stage transcriptional profile.

immunology↗

bioRxiv2021

Distinct nociresponsive region in mouse primary somatosensory cortex

Nociception, somatic discriminative aspects of pain, is represented in the primary somatosensory cortex (S1), as is touch, but the separation and the interaction of the two modalities within S1 remain unclear. Here, we show the spatially-distinct tactile and nociceptive processing in the granular barrel field (BF) and the adjacent dysgranular region (Dys) in mouse S1. Simultaneous recording of the multiunit activity across subregions reveals that Dys responses are selective to noxious input whereas those of BF are to tactile input. At the single neuron level, nociceptive information is represented separately from the tactile information in Dys layer 2/3. In contrast, both modalities are converged in a layer 5 neuron in each region. Interestingly, the two modalities interfere with each other in both regions. We further demonstrate that Dys, but not BF, activity is critically involved in neuropathic pain and pain behavior, and thus provide evidence that Dys is a center specialized for nociception in S1.

neuroscience↗