論文 - 佐々木　貴史

Subclinical hypopigmentation of the skin and hair in a Japanese patient with Hermansky-Pudlak syndrome type 3.

Saito S, Tanaka R, Sasaki T, Aoki S, Yasuhara R, Nakayama Y, Nagai T, Sonobe H, Ozawa Y, Kubo A

The Journal of dermatology 2019年10月

ISSN  0385-2407

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Sex-specific effects of apolipoprotein ε4 allele on mortality in very old and centenarian Japanese men.

Sasaki T, Nishimoto Y, Abe Y, Takayama M, Hirose N, Okano H, Arai Y

The journals of gerontology. Series A, Biological sciences and medical sciences 2019年10月

ISSN  1079-5006

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[Genetic Protective Factors for Dementia Isolated by Centenarian Researches].

Sasaki T, Nishimoto Y, Hirose N, Arai Y

Brain and nerve = Shinkei kenkyu no shinpo 71 （ 10 ） 1061 - 1070 2019年10月

ISSN  1881-6096

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Recovery of FRI-5 carbapenemase at a Japanese hospital where FRI-4 carbapenemase was discovered.

Uwamino Y, Kubota H, Sasaki T, Kosaka A, Furuhashi M, Uno S, Kudoh J, Murata M, Hasegawa N

The Journal of antimicrobial chemotherapy 74 （ 11 ） 3390 - 3392 2019年08月

ISSN  1460-2091

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Clonal Expansion of Second-Hit Cells with Somatic Recombinations or C>T Transitions Form Porokeratosis in MVD or MVK Mutant Heterozygotes.

Kubo A, Sasaki T, Suzuki H, Shiohama A, Aoki S, Sato S, Fujita H, Ono N, Umegaki-Arao N, Kawai T, Nakabayashi K, Hata K, Yamada D, Matsubara Y, Kosaki K, Amagai M

The Journal of investigative dermatology 2019年06月

ISSN  0022-202X

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Induced Pluripotent Stem Cells Reprogrammed with Three Inhibitors Show Accelerated Differentiation Potentials with High Levels of 2-Cell Stage Marker Expression

Nishihara K., Shiga T., Nakamura E., Akiyama T., Sasaki T., Suzuki S., Ko M., Tada N., Okano H., Akamatsu W.

Stem Cell Reports （Stem Cell Reports）  12 （ 2 ） 305 - 318 2019年02月

ISSN  22136711

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© 2019 The Authors Although pluripotent stem cells can generate various types of differentiated cells, it is unclear why lineage-committed stem/progenitor cells derived from pluripotent stem cells are decelerated and why the differentiation-resistant propensity of embryonic stem cell (ESC)/induced pluripotent stem cell (iPSC)-derived cells is predominant compared with the in vivo equivalents derived from embryonic/adult tissues. In this study, we demonstrated that iPSCs reprogrammed and maintained with three chemical inhibitors of the fibroblast growth factor 4-mitogen-activated protein kinase cascade and GSK3β (3i) could be differentiated into all three germ layers more efficiently than the iPSCs reprogrammed without the 3i chemicals, even though they were maintained with 3i chemicals once they were reprogrammed. Although the iPSCs reprogrammed with 3i had increased numbers of Zscan4-positive cells, the Zscan4-positive cells among iPSCs that were reprogrammed without 3i did not have an accelerated differentiation ability. These observations suggest that 3i exposure during the reprogramming period determines the accelerated differentiation/maturation potentials of iPSCs that are stably maintained at the distinct state.

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APOE Alleles and extreme human longevity

Sebastiani P., Gurinovich A., Nygaard M., Sasaki T., Sweigart B., Bae H., Andersen S., Villa F., Atzmon G., Christensen K., Arai Y., Barzilai N., Puca A., Christiansen L., Hirose N., Perls T.

Journals of Gerontology - Series A Biological Sciences and Medical Sciences （Journals of Gerontology - Series A Biological Sciences and Medical Sciences）  74 （ 1 ） 44 - 51 2019年01月

ISSN  10795006

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© 2018 The Author(s). Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. We assembled a collection of 28,297 participants from seven studies of longevity and healthy aging comprising New England Centenarian, Long Life Family, Longevity Gene Population, Southern Italian Centenarian, Japanese Centenarian, the Danish Longevity, and the Health and Retirement Studies to investigate the association between the APOE alleles ϵ 2 ϵ 3 and ϵ 4 and extreme human longevity and age at death. By using three different genetic models and two definitions of extreme longevity based on either a threshold model or age at death, we show that ϵ 4 is associated with a substantially decreased odds for extreme longevity, and increased risk for death that persists even beyond ages reached by less than 1% of the population. We also show that carrying the ϵ 2 ϵ 2 or ϵ 2 ϵ 3 genotype is associated with significantly increased odds to reach extreme longevity, with decreased risk for death compared with carrying the genotype ϵ 3 ϵ 3 but with only a modest reduction in risk for death beyond an age reached by less than 1% of the population.

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The desmosome is a mesoscale lipid raft–like membrane domain

Lewis J., Caldara A., Zimmer S., Stahley S., Seybold A., Strong N., Frangakis A., Levental I., Wahl J., Mattheyses A., Sasaki T., Nakabayashi K., Hata K., Matsubara Y., Ishida-Yamamoto A., Amagai M., Kubo A., Kowalczyk A.

Molecular Biology of the Cell （Molecular Biology of the Cell）  30 （ 12 ） 1390 - 1405 2019年

ISSN  10591524

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© 2019 Lewis, Caldara, et al. Desmogleins (Dsgs) are cadherin family adhesion molecules essential for epidermal integrity. Previous studies have shown that desmogleins associate with lipid rafts, but the significance of this association was not clear. Here, we report that the desmoglein transmembrane domain (TMD) is the primary determinant of raft association. Further, we identify a novel mutation in the DSG1 TMD (G562R) that causes severe dermatitis, multiple allergies, and metabolic wasting syndrome. Molecular modeling predicts that this G-to-R mutation shortens the DSG1 TMD, and experiments directly demonstrate that this mutation compromises both lipid raft association and desmosome incorporation. Finally, cryo-electron tomography indicates that the lipid bilayer within the desmosome is ∼10% thicker than adjacent regions of the plasma membrane. These findings suggest that differences in bilayer thickness influence the organization of adhesion molecules within the epithelial plasma membrane, with cadherin TMDs recruited to the desmosome via the establishment of a specialized mesoscale lipid raft–like membrane domain.

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Deep whole-genome sequencing reveals recent selection signatures linked to evolution and disease risk of Japanese

Okada Y., Momozawa Y., Sakaue S., Kanai M., Ishigaki K., Akiyama M., Kishikawa T., Arai Y., Sasaki T., Kosaki K., Suematsu M., Matsuda K., Yamamoto K., Kubo M., Hirose N., Kamatani Y.

Nature Communications （Nature Communications）  9 （ 1 ） 1631 2018年12月

ISSN  2041-1723

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© 2018 The Author(s). Understanding natural selection is crucial to unveiling evolution of modern humans. Here, we report natural selection signatures in the Japanese population using 2234 high-depth whole-genome sequence (WGS) data (25.9×). Using rare singletons, we identify signals of very recent selection for the past 2000-3000 years in multiple loci (ADH cluster, MHC region, BRAP-ALDH2, SERHL2). In large-scale genome-wide association study (GWAS) dataset (n = 171,176), variants with selection signatures show enrichment in heterogeneity of derived allele frequency spectra among the geographic regions of Japan, highlighted by two major regional clusters (Hondo and Ryukyu). While the selection signatures do not show enrichment in archaic hominin-derived genome sequences, they overlap with the SNPs associated with the modern human traits. The strongest overlaps are observed for the alcohol or nutrition metabolism-related traits. Our study illustrates the value of high-depth WGS to understand evolution and their relationship with disease risk.

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Intragenic copy number variation within human epiplakin 1 (EPPK1) generates variation of molecular size of epiplakin

Ishikawa Kazushi, Furuhashi Mie, Sasaki Takashi, Kudoh Jun, Tsuchisaka Atsunari, Hashimoto Takashi, Sasaki Takako, Yoshioka Hidekatsu, Eshima Nobuoki, Matsuda-Hirose Haruna, Sakai Takashi, Hatano Yutaka, Fujiwara Sakuhei

Journal of Dermatological Science 91 （ 2 ） 228 - 231 2018年08月

ISSN  0923-1811

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HER2 heterogeneity is associated with poor survival in HER2-positive breast cancer

Hosonaga M., Arima Y., Sampetrean O., Komura D., Koya I., Sasaki T., Sato E., Okano H., Kudoh J., Ishikawa S., Saya H., Ishikawa T.

International Journal of Molecular Sciences （International Journal of Molecular Sciences）  19 （ 8 ）  2018年08月

ISSN  1661-6596

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© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Intratumoral human epidermal growth factor receptor 2 (HER2) heterogeneity has been reported in 16–36% of HER2-positive breast cancer and its clinical impact is under discussion. We examined the biological effects of HER2-heterogeneity on mouse models and analyzed metastatic brains by RNA sequence analysis. A metastatic mouse model was developed using 231-Luc (triple negative cells) and 2 HER2-positive cell lines, namely, HER2-60 and HER2-90 which showed heterogeneous and monotonous HER2 expressions, respectively. Metastatic lesions developed in 3 weeks in all the mice injected with HER2-60 cells, and in 69% of the mice injected with HER2-90 and 87.5% of the mice injected with 231-Luc. The median survival days of mice injected with 231-Luc, HER2-60, and HER2-90 cells were 29 (n = 24), 24 (n = 22) and 30 (n = 13) days, respectively. RNA sequence analysis showed that CASP-1 and its related genes were significantly downregulated in metastatic brain tumors with HER2-60 cells. The low expression of caspase-1 could be a new prognostic biomarker for early relapse in HER2-positive breast cancer.

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A familial case of nail patella syndrome with a heterozygous in-frame indel mutation in the LIM domain of LMX1B

Mukai Miho, Fujita Harumi, Umegaki-Arao Noriko, Sasaki Takashi, Yasuda-Sekiguchi Fumiyo, Isojima Tsuyoshi, Kitanaka Sachiko, Amagai Masayuki, Kubo Akiharu

Journal of Dermatological Science 90 （ 1 ） 90 - 93 2018年04月

ISSN  0923-1811

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<p>Nail patella syndrome is a autosomal dominant disorder caused by a genetic alteration in LMX1B. We identified a novel heterozygous in-frame indel mutation of LMX1B in a family of Nail patella syndrome. Impaired transcriptional activity but not dominant negative effect of mutant LMX1B were revealed using a transcriptional reporter assay, indicating that the mutation caused nail patella syndrome in this family via haploinsufficiency of the transcriptional activity of LMX1B.</p>

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Junctional epidermolysis bullosa without pyloric atresia due to a homozygous missense mutation in ITGB4

Yoshida Kenji, Sadamoto Mariko, Sasaki Takashi, Kubo Akiharu, Ishiko Akira

Journal of Dermatology 2018年01月

ISSN  0385-2407

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Demographic, phenotypic, and genetic characteristics of centenarians in Okinawa and Honshu, Japan: Part 2 Honshu, Japan

Arai, Y., Sasaki, T. and Hirose, N.

Mech Ageing Dev 165 （ Pt B ） 80 - 85 2017年07月

ISSN  1872-6216

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The scope and purpose of this review was to summarize the aims, methods, findings, and future of centenarian and (semi)-supercentenarian studies in Japan, particularly those from our own interdisciplinary laboratory. Medically, approximately 97% of centenarians contract chronic diseases including hypertension and gastrointestinal disease; however, they present with few cardiovascular risk factors. The low prevalence of diabetes mellitus and carotid atherosclerotic plaques is peculiarities of centenarians, which could be associated with high adiponectin levels. While conducting the Tokyo centenarian study (TCS), we found that only 20% of centenarians enjoyed physical and cognitive independence at the age of 100 years, although most remained independent in daily living until into their 90s. Those who maintained physical independence at 100 years of age were highly likely to become semi-supercentenarians (over 105 years) or even supercentenarians (beyond 110 years). We also describe parts of results of the Japan Semi-supercentenarian Study (JSS), which showed that the suppression of chronic inflammation is an important driver of successful aging at extreme old age. Telomere maintenance and an extremely low frequency of APOE-epsilon4 alleles are genetic peculiarities of (semi)-supercentenarians. The available data confirm our conviction that semi-supercentenarians are a more appropriate model for the study of human longevity.

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Novel nonsense mutation in SERPINB7 and the treatment of foot odor in a patient with Nagashima-type palmoplantar keratosis

Katsuno, M., Shiohama, A., Aoki, S., Kitamura, H., Sasaki, T., Amagai, M. and Kubo, A.

J Dermatol 44 （ 7 ） e146 - e147 2017年07月

ISSN  1346-8138

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Association study of childhood food allergy with genome-wide association studies-discovered loci of atopic dermatitis and eosinophilic esophagitis

Hirota, T., Nakayama, T., Sato, S., Yanagida, N., Matsui, T., Sugiura, S., Takaoka, Y., Hizawa, N., Fujieda, S., Miyatake, A., Sasaki, T., Amagai, M., Doi, S., Ito, K., Ebisawa, M. and Tamari, M.

J Allergy Clin Immunol 2017年06月

ISSN  1097-6825

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Somatic HRAS p.G12S mosaic mutation causes unilaterally distributed epidermal nevi, woolly hair and palmoplantar keratosis

Honda, A., Umegaki-Arao, N., Sasaki, T., Nakabayashi, K., Hata, K., Matsubara, Y., Tanikawa, A., Amagai, M. and Kubo, A.

J Dermatol 44 （ 6 ） e109 - e110 2017年06月

ISSN  1346-8138

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Distinct phenotype of epidermolysis bullosa simplex with infantile migratory circinate erythema due to frameshift mutations in the V2 domain of KRT5

Kumagai, Y., Umegaki-Arao, N., Sasaki, T., Nakamura, Y., Takahashi, H., Ashida, A., Tsunemi, Y., Kawashima, M., Shimizu, A., Ishiko, A., Nakamura, K., Tsuchihashi, H., Amagai, M. and Kubo, A.

J Eur Acad Dermatol Venereol 31 （ 5 ） e241 - e243 2017年05月

ISSN  1468-3083

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Inflammatory Linear Verrucous Epidermal Nevus with a Postzygotic GJA1 Mutation Is a Mosaic Erythrokeratodermia Variabilis et Progressiva

Umegaki-Arao Noriko, Sasaki Takashi, Fujita Harumi, Aoki Satomi, Kameyama Kaori, Amagai Masayuki, Seishima Mariko, Kubo Akiharu

Journal of Investigative Dermatology 137 （ 4 ） 967 - 970 2017年04月

ISSN  0022-202X

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Inflammatory Linear Verrucous Epidermal Nevus with a Postzygotic GJA1 Mutation Is a Mosaic Erythrokeratodermia Variabilis et Progressiva

Umegaki-Arao, N., Sasaki, T., Fujita, H., Aoki, S., Kameyama, K., Amagai, M., Seishima, M. and Kubo, A.

J Invest Dermatol 137 （ 4 ） 967 - 970 2017年04月

ISSN  1523-1747

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