Biology subjects

Matsubara, H.

Publications and source records attributed to Matsubara, H..

7 recordsLinked to original sources

bioRxiv2025

Distinct dermal fibroblasts direct mechano-chemical signaling to the epidermis during pregnancy

Dermal fibroblasts alter extracellular matrix (ECM) and tissue mechanics dynamically in wound healing and fibrosis, however, are understudied in healthy skin remodeling across life stages. Here, by conducting spatio-temporal transcriptomics, we identified Cdh4+ dermal fibroblast subpopulation that remodels ECM and converts mechano-to-chemical signals to promote epidermal stem cell proliferation in expanding abdominal skin of pregnant mice. Mechanistically, Cdh4+ fibroblasts produce a pregnancy-responsive matrisome, resulting in denser and stiffer dermal fibrils. These fibroblasts then sense the stiffened substrate and convert the mechanical input into a chemical output via the YAP1-TGF{beta}2 axis, leading to the proliferation of epidermal stem cells via TGF{beta} receptor in the expanding skin. Thus, Cdh4+ fibroblasts fine-tune the dermal mechanofield and act as a mechanical-to-chemical signal conversion hub in healthy skin expansion.

developmental biology↗

bioRxiv2025

Lipid composition effects on the number and size of liposomes formed by the inverted emulsion method

Liposomes have been widely employed as membrane scaffolds in the construction of minimal cell models. In 2002, the inverted emulsion method was introduced as a novel technique for generating giant liposomes by transferring water-in-oil droplets across an oil/water interface. This technique enables the encapsulation of purified proteins or cytoplasmic extracts into cell-sized liposomes under physiological buffer conditions, and has since become a cornerstone in bottom-up synthetic biology. Despite its broad application over the past two decades, the effects of lipid composition on the production yield and size distribution of liposomes generated by the inverted emulsion method remain largely unknown. In this study, we systematically investigated the effects of phospholipid composition on the production yield and size distribution of liposomes generated using the inverted emulsion method. We used a natural phosphatidylcholine purified from chicken egg yolk (egg PC) as the base membrane component, and examined the extent to which substituting a fraction of egg PC with other phospholipids--differing in net electric charge and/or the molecular weight of their hydrophilic head groups--affects the number and size distribution of liposomes. We found that a 10% replacement of egg PC with charged phospholipids significantly enhances the production yield of liposomes by approximately tenfold, transformed by both the natural gravitational force and the greater force applied by centrifugation. In addition, lipids with smaller head groups slightly enhance the production yield in both methods. Lipids with larger head groups also slightly enhance the production yield and promote the formation of larger liposomes in the natural sedimentation method, but these effects are diminished in the centrifugal sedimentation method, presumably due to the strong centrifugal force. These findings provide valuable guidelines for optimizing preparation protocols for minimal cell models.

biophysics↗

bioRxiv2024

Novel function of Hox13 in regulating outgrowth of the newt hindlimb bud through interaction with Fgf10 and Tbx4

5Hox genes regulate pattern formation along the axes of the limb. Previously, we showed that Hoxa13/Hoxd13 double mutant newts lacked all digits of the forelimbs during development and regeneration, showing that newt Hox13 is necessary for digit formation in development and regeneration. In addition, we found another unique phenotype. A part of the Hox13 crispant newts showed hindlimb defects, in which whole or almost whole hindlimbs were lost, suggesting a novel function of Hox13 in limb development. Using germline mutants, we showed that mutation in Hox13 led to hindlimb defects. The limb buds of Hox13 crispants formed, however, did not show outgrowth. Expression of Fgf10 and Tbx4, which are involved in limb outgrowth, decreased in the hindlimb buds of Hox13 crispants. In addition, hindlimb defects were observed in both Fgf10 and Tbx4 crispant newts. Finally, Fgf10 and Tbx4 interacted with Hox13 genetically. Our results revealed a novel function of Hox13 in regulating the outgrowth of the newt hindlimb bud through interaction with Fgf10 and Tbx4.

developmental biology↗

bioRxiv2023

ECM degradation in the stump region induced by Fgf during functional joint regeneration in frogs

Previous studies indicated the importance of the reciprocal interactions between residual tissues in the stump and the newly formed blastema for achieving functional joint regeneration after amputation at the joint level in newts. This reciprocal interaction during regeneration was named "reintegration". When this reintegration mechanism was evoked in Xenopus leavis, regeneration of a functional joint was induced in frogs. Interestingly, degradation of extracellular matrix (ECM) in the remaining joint cartilage was observed during regeneration in both newts and frogs. Histological and gene expression analyses suggested that the degradation of Type II collagen in the cartilage of the articular head might be performed by matrix metalloproteases (Mmps) which were transiently expressed after amputation. We found that fibroblast growth factor (Fgf) induced Mmps expression in the cartilage of the articular head. These results support the possibility that the Fgf signal induces ECM degradation in joint tissues via Mmps expression and that the ECM degradation and subsequent bone morphogenetic protein (Bmp) secretion promote cell proliferation, migration, and differentiation of the cells in the blastema to achieve functional joint regeneration.

developmental biology↗

bioRxiv2019

Clustering by phenotype and genome-wide association study in autism

BackgroundAutism spectrum disorder (ASD) has phenotypically and genetically heterogeneous characteristics. A simulation study demonstrated that attempts to categorize patients with a complex disease into more homogeneous subgroups could have more power to elucidate hidden heritability. MethodsWe conducted cluster analyses using the k-means algorithm with a cluster number of 15 based on phenotypic variables from the Simons Simplex Collection (SSC). As a preliminary study, we conducted a conventional genome-wide association study (GWAS) with a dataset of 597 ASD cases and 370 controls. In the second step, we divided cases based on the clustering results and conducted GWAS in each of the subgroups vs controls (cluster-based GWAS). We also conducted cluster-based GWAS on another SSC dataset of 712 probands and 354 controls in the replication stage. ResultsIn the preliminary study, we observed no significant associations. In the second step of cluster-based GWASs, we identified 65 chromosomal loci, which included 30 intragenic loci located in 21 genes and 35 intergenic loci that satisfied the threshold of P<5.0x10-8. Some of these loci were located within or near previously reported candidate genes for ASD: CDH5, CNTN5, CNTNAP5, DNAH17, DPP10, DSCAM, FOXK1, GABBR2, GRIN2A5, ITPR1, NTM, SDK1, SNCA and SRRM4. Of these 65 significant chromosomal loci, rs11064685 located within the SRRM4 gene had a significantly different distribution in the cases vs. controls in the replication cohort. ConclusionsThese findings suggest that clustering may successfully identify subgroups with relatively homogeneous disease etiologies. Further cluster validation and replication studies are warranted in larger cohorts.

neuroscience↗

bioRxiv2019

Autologous adipose-derived stem cell transplantation enhances healing of wound with exposed bone in a rat model

ObjectivesSoft tissue wounds with exposed bone often require extended healing times and can be associated with severe complications. We describe the ability of artificial dermis with autogenic adipose-derived stem cells (ADSCs) to promote the healing of wounds with exposed bone in a rat model.\n\nMethodsAdipose tissues harvested from the bilateral inguinal regions of Wistar rats were used as ADSCs. Rats were randomly divided into control and ADSC groups to investigate the efficacy of ADSC transplantation for wound healing (n=20 per group). Soft tissue defects were created on the heads of the rats and were covered with artificial dermis with or without the seeded ADSCs. Specimens from these rats were evaluated using digital image analysis, histology, immunohistochemistry, cell labeling, and real-time reverse-transcription polymerase chain reaction (Real-time RT-PCR).\n\nResultsThe average global wound area was significantly smaller in the ADSC group than in the control group on days 3, 7, and 14 after surgery (p<0.05). After 14 days, the blood vessel density in the wound increased by 1.6-fold in the ADSC group compared with that in the control group (p<0.01). Real-time RT-PCR results showed higher Fgfb and Vegf expression levels at all time points, and higher Tgfb1 and Tgfb3 expression levels until 14 days after surgery, in the ADSC group than in the control group (p<0.05).\n\nConclusionsIn wounds with exposed bone, autogenic ADSCs can promote vascularization and wound healing. Use of this cell source has multiple benefits, including convenient clinical application and lack of ethical concerns.

animal behavior and cognition↗

bioRxiv2019

Management of family relationship informationfor a three-generation cohort study

A system for inputting and storing family information, named \"BirThree Enrollment,\" was developed to promote a birth and three-generation cohort study (BirThree Cohort Study), and this system was operated successfully. In the study, it was necessary to satisfy many operational demands. Input information is overwritten and changed continuously. Complex kinship information must be quickly and accurately input and corrected, and information on those families not yet recruited must be retrieved. For these purposes, many devices are needed, from an input interface to the internal data structure. In the field of genetic statistics, a simple standard expressive form is used for describing family structure. This form has sufficient information for genetics; however, we developed this form further for our purposes in conducting the BirThree Cohort Study. To provide information about family roles as required in the BirThree Cohort Study, we expanded the data structure, and constructed the system that is able to be used for the daily operation. In our system, family pedigree information is stored along with initial clinical information, and enabled the input of all self-reported information to the data base. Operators are able to input this family information before the day is out. As a result, when recruitment is completed, family information will be completed concurrently. Therefore, it is possible to immediately know a certain persons family structure. By using our system, data correction was improved dramatically, and the system was operated successfully. This study is the first report of the method for storing three generations of family data.

epidemiology↗