Biology subjects

Miyajima, H.

Publications and source records attributed to Miyajima, H..

3 recordsLinked to original sources

bioRxiv2024

Aberrant axon initial segment is an indicator for task-independent neural activity in autism model mice

Autism spectrum disorder (ASD) is a developmental disorder characterized by impairments in several communicative behaviors. Identification of biomarkers for ASD based on task-independent neural activity has been elusive. The axonal initial segment (AIS), located at the proximal part of the axon, is crucial for initiating action potentials (APs) and adaptable through activity-dependent AIS plasticity. In our study, we discovered decrease in AIS length in layer V pyramidal neurons (PyNs) of the prelimbic cortex (PrL) and increase in layer II/III PyNs in the somatosensory cortex of duplicated human 15q11-13 region (15q dup) ASD model mice. Electrophysiological studies using whole-cell patch-clamp recordings in the PrL revealed diminished ability to generate APs. We discovered lack of AIS plasticity in 15q dup mice under conditions of elevated potassium chloride. Retrograde tracing demonstrated that AIS shortening depends on the projection targets. These results indicate that activity-dependent aberrant AIS structures can serve as indicators of altered task-independent neural activity in ASD mouse models.

neuroscience↗

bioRxiv2022

Distinct chaperonopathy in skeletal muscle associated with the dominant variant in DNAJB4

DnaJ homolog, subfamily B, member 4, a member of the heat shock protein 40 chaperones encoded by DNAJB4, is highly expressed in myofibers. We identified a heterozygous c.270 T>A (p.F90L) variant in DNAJB4 in a family with a dominantly inherited distal myopathy, in which affected members have specific features on muscle pathology represented by the presence of cytoplasmic inclusions and the accumulation of desmin, p62, HSP70 and DNAJB4 predominantly in type 1 fibers. Both Dnajb4- F90L knock-in and knockout mice developed muscle weakness and recapitulated the patient muscle pathology in the soleus muscle, where DNAJB4 has the highest expression. These data indicate that the identified variant is causative resulting in defective chaperone function and selective muscle degeneration in specific muscle fibers. This study demonstrates the importance of DNAJB4 in skeletal muscle proteostasis by identifying the associated chaperonopathy.

neuroscience↗

bioRxiv2020

Characterization of human embryonic stem cells in animal component-free medium

Clinical use of human embryonic stem cells (ESCs) as a raw material requires good manufacturing practice-compliant axillary materials such as culture medium. To this end, animal components should not be used and contamination of virus/bacteria/fungus and allergens are a concern. In addition, animal components such as albumin and fetal bovine serum pose difficulties such as a lot-to-lot variation. However, only a limited number of animal component-free media have been developed to date. In this study, we investigated whether SEES2 ESCs can be stably propagated for 16 passages (54 population doublings) over a period of 60 days in a newly established Stem-Partner(R) ACF medium. SEES2 ESC maintained their intact karyotype, i.e. 46,XX, and their undifferentiated phenotypes after long-term culture. An in vitro differentiation assay revealed that SEES2 ESCs exhibited multipotency, i.e. endodermal, mesodermal and ectodermal differentiation. Subcutaneous implantation of SEES2 ESCs generated mature teratomas without malignant transformation. These results show that SEES2 ESCs in the Stem-Partner(R) ACF medium can be used to establish master cell banks for future regenerative medicine as well as other ESCs in the previously reported culture medium.

cell biology↗