14 results on '"Ishigaki, Kazuyoshi"'
Search Results
2. The genetic basis of autoimmunity seen through the lens of T cell functional traits
- Author
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Lagattuta, Kaitlyn A., Park, Hannah L., Rumker, Laurie, Ishigaki, Kazuyoshi, Nathan, Aparna, and Raychaudhuri, Soumya
- Published
- 2024
- Full Text
- View/download PDF
3. Quantification of escape from X chromosome inactivation with single-cell omics data reveals heterogeneity across cell types and tissues
- Author
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Charoensawan, Varodom, Hon, Chung-Chau, Majumder, Partha P., Matangkasombut, Ponpan, Park, Woong-Yang, Prabhakar, Shyam, Shin, Jay W., Carninci, Piero, Chambers, John C., Loh, Marie, Pithukpakorn, Manop, Suktitipat, Bhoom, Yamamoto, Kazuhiko, Rajagopalan, Deepa, Rayan, Nirmala Arul, Sankaran, Shvetha, Chantaraamporn, Juthamard, Chatterjee, Ankita, Ghosh, Supratim, Han, Kyung Yeon, Jevapatarakul, Damita, Nguantad, Sarintip, Sarkar, Sumanta, Thungsatianpun, Narita, Abe, Mai, Furukawa, Seiko, Inoue, Gyo, Myouzen, Keiko, Oh, Jin-Mi, Suzuki, Akari, Ando, Yoshinari, Kojima, Miki, Kouno, Tsukasa, Lim, Jinyeong, Maitra, Arindam, Tan, Le Min, Venkatesh, Prasanna Nori, Choi, Murim, Park, Jong-Eun, Buyamin, Eliora Violain, Kock, Kian Hong, Xuan Lin, Quy Xiao, Moody, Jonathan, Sonthalia, Radhika, Ishigaki, Kazuyoshi, Nakano, Masahiro, Okada, Yukinori, Tomofuji, Yoshihiko, Ho Namkoong, Edahiro, Ryuya, Takano, Tomomi, Nishihara, Hiroshi, Shirai, Yuya, Sonehara, Kyuto, Tanaka, Hiromu, Azekawa, Shuhei, Mikami, Yohei, Lee, Ho, Hasegawa, Takanori, Okudela, Koji, Okuzaki, Daisuke, Motooka, Daisuke, Kanai, Masahiro, Naito, Tatsuhiko, Yamamoto, Kenichi, Wang, Qingbo S., Saiki, Ryunosuke, Ishihara, Rino, Matsubara, Yuta, Hamamoto, Junko, Hayashi, Hiroyuki, Yoshimura, Yukihiro, Tachikawa, Natsuo, Yanagita, Emmy, Hyugaji, Takayoshi, Shimizu, Eigo, Katayama, Kotoe, Kato, Yasuhiro, Morita, Takayoshi, Takahashi, Kazuhisa, Harada, Norihiro, Naito, Toshio, Hiki, Makoto, Matsushita, Yasushi, Takagi, Haruhi, Aoki, Ryousuke, Nakamura, Ai, Harada, Sonoko, Sasano, Hitoshi, Kabata, Hiroki, Masaki, Katsunori, Kamata, Hirofumi, Ikemura, Shinnosuke, Chubachi, Shotaro, Okamori, Satoshi, Terai, Hideki, Morita, Atsuho, Asakura, Takanori, Sasaki, Junichi, Morisaki, Hiroshi, Uwamino, Yoshifumi, Nanki, Kosaku, Uchida, Sho, Uno, Shunsuke, Nishimura, Tomoyasu, Ishiguro, Takashi, Isono, Taisuke, Shibata, Shun, Matsui, Yuma, Hosoda, Chiaki, Takano, Kenji, Nishida, Takashi, Kobayashi, Yoichi, Takaku, Yotaro, Takayanagi, Noboru, Ueda, Soichiro, Tada, Ai, Miyawaki, Masayoshi, Yamamoto, Masaomi, Yoshida, Eriko, Hayashi, Reina, Nagasaka, Tomoki, Arai, Sawako, Kaneko, Yutaro, Sasaki, Kana, Tagaya, Etsuko, Kawana, Masatoshi, Arimura, Ken, Takahashi, Kunihiko, Anzai, Tatsuhiko, Ito, Satoshi, Endo, Akifumi, Uchimura, Yuji, Miyazaki, Yasunari, Honda, Takayuki, Tateishi, Tomoya, Tohda, Shuji, Ichimura, Naoya, Sonobe, Kazunari, Sassa, Chihiro Tani, Nakajima, Jun, Nakano, Yasushi, Nakajima, Yukiko, Anan, Ryusuke, Arai, Ryosuke, Kurihara, Yuko, Harada, Yuko, Nishio, Kazumi, Ueda, Tetsuya, Azuma, Masanori, Saito, Ryuichi, Sado, Toshikatsu, Miyazaki, Yoshimune, Sato, Ryuichi, Haruta, Yuki, Nagasaki, Tadao, Yasui, Yoshinori, Hasegawa, Yoshinori, Mutoh, Yoshikazu, Kimura, Tomoki, Sato, Tomonori, Takei, Reoto, Hagimoto, Satoshi, Noguchi, Yoichiro, Yamano, Yasuhiko, Sasano, Hajime, Ota, Sho, Nakamori, Yasushi, Yoshiya, Kazuhisa, Saito, Fukuki, Yoshihara, Tomoyuki, Wada, Daiki, Iwamura, Hiromu, Kanayama, Syuji, Maruyama, Shuhei, Yoshiyama, Takashi, Ohta, Ken, Kokuto, Hiroyuki, Ogata, Hideo, Tanaka, Yoshiaki, Arakawa, Kenichi, Shimoda, Masafumi, Osawa, Takeshi, Tateno, Hiroki, Hase, Isano, Yoshida, Shuichi, Suzuki, Shoji, Kawada, Miki, Horinouchi, Hirohisa, Saito, Fumitake, Mitamura, Keiko, Hagihara, Masao, Ochi, Junichi, Uchida, Tomoyuki, Baba, Rie, Arai, Daisuke, Ogura, Takayuki, Takahashi, Hidenori, Hagiwara, Shigehiro, Nagao, Genta, Konishi, Shunichiro, Nakachi, Ichiro, Murakami, Koji, Yamada, Mitsuhiro, Sugiura, Hisatoshi, Sano, Hirohito, Matsumoto, Shuichiro, Kimura, Nozomu, Ono, Yoshinao, Baba, Hiroaki, Suzuki, Yusuke, Nakayama, Sohei, Masuzawa, Keita, Namba, Shinichi, Suzuki, Ken, Naito, Yoko, Liu, Yu-Chen, Takuwa, Ayako, Sugihara, Fuminori, Wing, James B., Sakakibara, Shuhei, Hizawa, Nobuyuki, Shiroyama, Takayuki, Miyawaki, Satoru, Kawamura, Yusuke, Nakayama, Akiyoshi, Matsuo, Hirotaka, Yuichi, Maeda, Nii, Takuro, Noda, Yoshimi, Niitsu, Takayuki, Adachi, Yuichi, Enomoto, Takatoshi, Amiya, Saori, Hara, Reina, Yamaguchi, Yuta, Murakami, Teruaki, Kuge, Tomoki, Matsumoto, Kinnosuke, Yamamoto, Yuji, Yamamoto, Makoto, Yoneda, Midori, Kishikawa, Toshihiro, Yamada, Shuhei, Kawabata, Shuhei, Kijima, Noriyuki, Takagaki, Masatoshi, Sasa, Noah, Ueno, Yuya, Suzuki, Motoyuki, Takemoto, Norihiko, Eguchi, Hirotaka, Fukusumi, Takahito, Imai, Takao, Fukushima, Munehisa, Kishima, Haruhiko, Inohara, Hidenori, Tomono, Kazunori, Kato, Kazuto, Takahashi, Meiko, Matsuda, Fumihiko, Hirata, Haruhiko, Takeda, Yoshito, Koh, Hidefumi, Manabe, Tadashi, Funatsu, Yohei, Ito, Fumimaro, Fukui, Takahiro, Shinozuka, Keisuke, Kohashi, Sumiko, Miyazaki, Masatoshi, Shoko, Tomohisa, Kojima, Mitsuaki, Adachi, Tomohiro, Ishikawa, Motonao, Takahashi, Kenichiro, Inoue, Takashi, Hirano, Toshiyuki, Kobayashi, Keigo, Takaoka, Hatsuyo, Watanabe, Kazuyoshi, Miyazawa, Naoki, Kimura, Yasuhiro, Sado, Reiko, Sugimoto, Hideyasu, Kamiya, Akane, Kuwahara, Naota, Fujiwara, Akiko, Matsunaga, Tomohiro, Sato, Yoko, Okada, Takenori, Hirai, Yoshihiro, Kawashima, Hidetoshi, Narita, Atsuya, Niwa, Kazuki, Sekikawa, Yoshiyuki, Nishi, Koichi, Nishitsuji, Masaru, Tani, Mayuko, Suzuki, Junya, Nakatsumi, Hiroki, Ogura, Takashi, Kitamura, Hideya, Hagiwara, Eri, Murohashi, Kota, Okabayashi, Hiroko, Mochimaru, Takao, Nukaga, Shigenari, Satomi, Ryosuke, Oyamada, Yoshitaka, Mori, Nobuaki, Baba, Tomoya, Fukui, Yasutaka, Odate, Mitsuru, Mashimo, Shuko, Makino, Yasushi, Yagi, Kazuma, Hashiguchi, Mizuha, Kagyo, Junko, Shiomi, Tetsuya, Fuke, Satoshi, Saito, Hiroshi, Tsuchida, Tomoya, Fujitani, Shigeki, Takita, Mumon, Morikawa, Daiki, Yoshida, Toru, Izumo, Takehiro, Inomata, Minoru, Kuse, Naoyuki, Awano, Nobuyasu, Tone, Mari, Ito, Akihiro, Nakamura, Yoshihiko, Hoshino, Kota, Maruyama, Junichi, Ishikura, Hiroyasu, Takata, Tohru, Odani, Toshio, Amishima, Masaru, Hattori, Takeshi, Shichinohe, Yasuo, Kagaya, Takashi, Kita, Toshiyuki, Ohta, Kazuhide, Sakagami, Satoru, Koshida, Kiyoshi, Hayashi, Kentaro, Shimizu, Tetsuo, Kozu, Yutaka, Hiranuma, Hisato, Gon, Yasuhiro, Izumi, Namiki, Nagata, Kaoru, Ueda, Ken, Taki, Reiko, Hanada, Satoko, Kawamura, Kodai, Ichikado, Kazuya, Nishiyama, Kenta, Muranaka, Hiroyuki, Nakamura, Kazunori, Hashimoto, Naozumi, Wakahara, Keiko, Koji, Sakamoto, Omote, Norihito, Ando, Akira, Kodama, Nobuhiro, Kaneyama, Yasunari, Shunsuke, Maeda, Kuraki, Takashige, Matsumoto, Takemasa, Yokote, Koutaro, Nakada, Taka-Aki, Abe, Ryuzo, Oshima, Taku, Shimada, Tadanaga, Harada, Masahiro, Takahashi, Takeshi, Ono, Hiroshi, Sakurai, Toshihiro, Shibusawa, Takayuki, Kimizuka, Yoshifumi, Kawana, Akihiko, Sano, Tomoya, Watanabe, Chie, Suematsu, Ryohei, Sageshima, Hisako, Yoshifuji, Ayumi, Ito, Kazuto, Takahashi, Saeko, Ishioka, Kota, Nakamura, Morio, Masuda, Makoto, Wakabayashi, Aya, Watanabe, Hiroki, Ueda, Suguru, Nishikawa, Masanori, Chihara, Yusuke, Takeuchi, Mayumi, Onoi, Keisuke, Shinozuka, Jun, Sueyoshi, Atsushi, Nagasaki, Yoji, Okamoto, Masaki, Ishihara, Sayoko, Shimo, Masatoshi, Tokunaga, Yoshihisa, Kusaka, Yu, Ohba, Takehiko, Isogai, Susumu, Ogawa, Aki, Inoue, Takuya, Fukuyama, Satoru, Eriguchi, Yoshihiro, Yonekawa, Akiko, Kan-o, Keiko, Matsumoto, Koichiro, Kanaoka, Kensuke, Ihara, Shoichi, Komuta, Kiyoshi, Inoue, Yoshiaki, Chiba, Shigeru, Yamagata, Kunihiro, Hiramatsu, Yuji, Kai, Hirayasu, Asano, Koichiro, Oguma, Tsuyoshi, Ito, Yoko, Hashimoto, Satoru, Yamasaki, Masaki, Kasamatsu, Yu, Komase, Yuko, Hida, Naoya, Tsuburai, Takahiro, Oyama, Baku, Takada, Minoru, Kanda, Hidenori, Kitagawa, Yuichiro, Fukuta, Tetsuya, Miyake, Takahito, Yoshida, Shozo, Ogura, Shinji, Abe, Shinji, Kono, Yuta, Togashi, Yuki, Takoi, Hiroyuki, Kikuchi, Ryota, Ogawa, Shinichi, Ogata, Tomouki, Ishihara, Shoichiro, Kanehiro, Arihiko, Ozaki, Shinji, Fuchimoto, Yasuko, Wada, Sae, Fujimoto, Nobukazu, Nishiyama, Kei, Terashima, Mariko, Beppu, Satoru, Yoshida, Kosuke, Narumoto, Osamu, Nagai, Hideaki, Ooshima, Nobuharu, Motegi, Mitsuru, Umeda, Akira, Miyagawa, Kazuya, Shimada, Hisato, Endo, Mayu, Ohira, Yoshiyuki, Watanabe, Masafumi, Inoue, Sumito, Igarashi, Akira, Sato, Masamichi, Sagara, Hironori, Tanaka, Akihiko, Ohta, Shin, Kimura, Tomoyuki, Shibata, Yoko, Tanino, Yoshinori, Nikaido, Takefumi, Minemura, Hiroyuki, Sato, Yuki, Yamada, Yuichiro, Hashino, Takuya, Shinoki, Masato, Iwagoe, Hajime, Takahashi, Hiroshi, Fujii, Kazuhiko, Kishi, Hiroto, Kanai, Masayuki, Imamura, Tomonori, Yamashita, Tatsuya, Yatomi, Masakiyo, Maeno, Toshitaka, Hayashi, Shinichi, Takahashi, Mai, Kuramochi, Mizuki, Kamimaki, Isamu, Tominaga, Yoshiteru, Ishii, Tomoo, Utsugi, Mitsuyoshi, Ono, Akihiro, Tanaka, Toru, Kashiwada, Takeru, Fujita, Kazue, Saito, Yoshinobu, Seike, Masahiro, Watanabe, Hiroko, Matsuse, Hiroto, Kodaka, Norio, Nakano, Chihiro, Oshio, Takeshi, Hirouchi, Takatomo, Makino, Shohei, Egi, Moritoki, Omae, Yosuke, Nannya, Yasuhito, Ueno, Takafumi, Katayama, Kazuhiko, Ai, Masumi, Fukui, Yoshinori, Kumanogoh, Atsushi, Sato, Toshiro, Hasegawa, Naoki, Tokunaga, Katsushi, Ishii, Makoto, Koike, Ryuji, Kitagawa, Yuko, Kimura, Akinori, Imoto, Seiya, Miyano, Satoru, Ogawa, Seishi, Kanai, Takanori, Fukunaga, Koichi, Takeshima, Yusuke, Tanaka, Kentaro, Koichi Matsuda, Yamanashi, Yuji, Furukawa, Yoichi, Morisaki, Takayuki, Murakami, Yoshinori, Kamatani, Yoichiro, Muto, Kaori, Nagai, Akiko, Nakamura, Yusuke, Obara, Wataru, Yamaji, Ken, Asai, Satoshi, Takahashi, Yasuo, Higashiue, Shinichi, Kobayashi, Shuzo, Yamaguchi, Hiroki, Nagata, Yasunobu, Wakita, Satoshi, Nito, Chikako, Iwasaki, Yu-ki, Murayama, Shigeo, Yoshimori, Kozo, Miki, Yoshio, Obata, Daisuke, Higashiyama, Masahiko, Masumoto, Akihide, Koga, Yoshinobu, Koretsune, Yukihiro, Yata, Tomohiro, Ogawa, Kotaro, Namkoong, Ho, Okuno, Tatsusada, Liu, Boxiang, Matsuda, Koichi, and Mochizuki, Hideki
- Published
- 2024
- Full Text
- View/download PDF
4. How can genetics analysis allow for early detection of rheumatoid arthritis
- Author
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Yamamoto, Kazuhiko, Ishigaki, Kazuyoshi, and Okada, Yukinori
- Published
- 2024
- Full Text
- View/download PDF
5. A genome-wide association study identified PTPN2 as a population-specific susceptibility gene locus for primary biliary cholangitis
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Hitomi, Yuki, primary, Ueno, Kazuko, additional, Aiba, Yoshihiro, additional, Nishida, Nao, additional, Kono, Michihiro, additional, Sugihara, Mitsuki, additional, Kawai, Yosuke, additional, Kawashima, Minae, additional, Khor, Seik-Soon, additional, Sugi, Kazuhiro, additional, Kouno, Hirotaka, additional, Kouno, Hiroshi, additional, Naganuma, Atsushi, additional, Iwamoto, Satoru, additional, Katsushima, Shinji, additional, Furuta, Kiyoshi, additional, Nikami, Toshiki, additional, Mannami, Tomohiko, additional, Yamashita, Tsutomu, additional, Ario, Keisuke, additional, Komatsu, Tatsuji, additional, Makita, Fujio, additional, Shimada, Masaaki, additional, Hirashima, Noboru, additional, Yokohama, Shiro, additional, Nishimura, Hideo, additional, Sugimoto, Rie, additional, Komura, Takuya, additional, Ota, Hajime, additional, Kojima, Motoyuki, additional, Nakamuta, Makoto, additional, Fujimori, Naoyuki, additional, Yoshizawa, Kaname, additional, Mano, Yutaka, additional, Takahashi, Hironao, additional, Hirooka, Kana, additional, Tsuruta, Satoru, additional, Sato, Takeaki, additional, Yamasaki, Kazumi, additional, Kugiyama, Yuki, additional, Motoyoshi, Yasuhide, additional, Suehiro, Tomoyuki, additional, Saeki, Akira, additional, Matsumoto, Kosuke, additional, Nagaoka, Shinya, additional, Abiru, Seigo, additional, Yatsuhashi, Hiroshi, additional, Ito, Masahiro, additional, Kawata, Kazuhito, additional, Takaki, Akinobu, additional, Arai, Kuniaki, additional, Arinaga, Teruko, additional, Abe, Masanori, additional, Harada, Masaru, additional, Taniai, Makiko, additional, Zeniya, Mikio, additional, Ohira, Hiromasa, additional, Shimoda, Shinji, additional, Komori, Atsumasa, additional, Tanaka, Atsushi, additional, Ishigaki, Kazuyoshi, additional, Nagasaki, Masao, additional, Tokunaga, Katsushi, additional, and Nakamura, Minoru, additional
- Published
- 2024
- Full Text
- View/download PDF
6. Long-read sequencing for 29 immune cell subsets reveals disease-linked isoforms
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30439244, Inamo, Jun, Suzuki, Akari, Ueda, Mahoko Takahashi, Yamaguchi, Kensuke, Nishida, Hiroshi, Suzuki, Katsuya, Kaneko, Yuko, Takeuchi, Tsutomu, Hatano, Hiroaki, Ishigaki, Kazuyoshi, Ishihama, Yasushi, Yamamoto, Kazuhiko, Kochi, Yuta, 30439244, Inamo, Jun, Suzuki, Akari, Ueda, Mahoko Takahashi, Yamaguchi, Kensuke, Nishida, Hiroshi, Suzuki, Katsuya, Kaneko, Yuko, Takeuchi, Tsutomu, Hatano, Hiroaki, Ishigaki, Kazuyoshi, Ishihama, Yasushi, Yamamoto, Kazuhiko, and Kochi, Yuta
- Abstract
Alternative splicing events are a major causal mechanism for complex traits, but they have been understudied due to the limitation of short-read sequencing. Here, we generate a full-length isoform annotation of human immune cells from an individual by long-read sequencing for 29 cell subsets. This contains a number of unannotated transcripts and isoforms such as a read-through transcript of TOMM40-APOE in the Alzheimer’s disease locus. We profile characteristics of isoforms and show that repetitive elements significantly explain the diversity of unannotated isoforms, providing insight into the human genome evolution. In addition, some of the isoforms are expressed in a cell-type specific manner, whose alternative 3’-UTRs usage contributes to their specificity. Further, we identify disease-associated isoforms by isoform switch analysis and by integration of several quantitative trait loci analyses with genome-wide association study data. Our findings will promote the elucidation of the mechanism of complex diseases via alternative splicing.
- Published
- 2024
7. Identification of telomere maintenance gene variations related to lung adenocarcinoma risk by genome‐wide association and whole genome sequencing analyses
- Author
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Shiraishi, Kouya, Takahashi, Atsushi, Momozawa, Yukihide, Daigo, Yataro, Kaneko, Syuzo, Kawaguchi, Takahisa, Kunitoh, Hideo, Matsumoto, Shingo, Horinouchi, Hidehito, Goto, Akiteru, Honda, Takayuki, Shimizu, Kimihiro, Torasawa, Masahiro, Takayanagi, Daisuke, Saito, Motonobu, Saito, Akira, Ohe, Yuichiro, Watanabe, Shun-ichi, Goto, Koichi, Tsuboi, Masahiro, Tsuchihara, Katsuya, Takata, Sadaaki, Aoi, Tomomi, Takano, Atsushi, Kobayashi, Masashi, Miyagi, Yohei, Tanaka, Kazumi, Suzuki, Hiroyuki, Maeda, Daichi, Yamaura, Takumi, Matsuda, Maiko, Shimada, Yoko, Mizuno, Takaaki, Sakamoto, Hiromi, Yoshida, Teruhiko, Goto, Yasushi, Yoshida, Tatsuya, Yamaji, Taiki, Sonobe, Makoto, Toyooka, Shinichi, Yoneda, Kazue, Masago, Katsuhiro, Tanaka, Fumihiro, Hara, Megumi, Fuse, Nobuo, Nishizuka, Satoshi S., Motoi, Noriko, Sawada, Norie, Nishida, Yuichiro, Kumada, Kazuki, Takeuchi, Kenji, Tanno, Kozo, Yatabe, Yasushi, Sunami, Kuniko, Hishida, Tomoyuki, Miyazaki, Yasunari, Ito, Hidemi, Amemiya, Mitsuhiro, Totsuka, Hirohiko, Nakayama, Haruhiko, Yokose, Tomoyuki, Ishigaki, Kazuyoshi, Nagashima, Toshiteru, Ohtaki, Yoichi, Imai, Kazuhiro, Takasawa, Ken, Minamiya, Yoshihiro, Kobayashi, Kazuma, Okubo, Kenichi, Wakai, Kenji, Shimizu, Atsushi, Yamamoto, Masayuki, Iwasaki, Motoki, Matsuda, Koichi, Inazawa, Johji, Shiraishi, Yuichi, Nishikawa, Hiroyoshi, Murakami, Yoshinori, Kubo, Michiaki, Matsuda, Fumihiko, Kamatani, Yoichiro, Hamamoto, Ryuji, Matsuo, Keitaro, Kohno, Takashi, Shiraishi, Kouya, Takahashi, Atsushi, Momozawa, Yukihide, Daigo, Yataro, Kaneko, Syuzo, Kawaguchi, Takahisa, Kunitoh, Hideo, Matsumoto, Shingo, Horinouchi, Hidehito, Goto, Akiteru, Honda, Takayuki, Shimizu, Kimihiro, Torasawa, Masahiro, Takayanagi, Daisuke, Saito, Motonobu, Saito, Akira, Ohe, Yuichiro, Watanabe, Shun-ichi, Goto, Koichi, Tsuboi, Masahiro, Tsuchihara, Katsuya, Takata, Sadaaki, Aoi, Tomomi, Takano, Atsushi, Kobayashi, Masashi, Miyagi, Yohei, Tanaka, Kazumi, Suzuki, Hiroyuki, Maeda, Daichi, Yamaura, Takumi, Matsuda, Maiko, Shimada, Yoko, Mizuno, Takaaki, Sakamoto, Hiromi, Yoshida, Teruhiko, Goto, Yasushi, Yoshida, Tatsuya, Yamaji, Taiki, Sonobe, Makoto, Toyooka, Shinichi, Yoneda, Kazue, Masago, Katsuhiro, Tanaka, Fumihiro, Hara, Megumi, Fuse, Nobuo, Nishizuka, Satoshi S., Motoi, Noriko, Sawada, Norie, Nishida, Yuichiro, Kumada, Kazuki, Takeuchi, Kenji, Tanno, Kozo, Yatabe, Yasushi, Sunami, Kuniko, Hishida, Tomoyuki, Miyazaki, Yasunari, Ito, Hidemi, Amemiya, Mitsuhiro, Totsuka, Hirohiko, Nakayama, Haruhiko, Yokose, Tomoyuki, Ishigaki, Kazuyoshi, Nagashima, Toshiteru, Ohtaki, Yoichi, Imai, Kazuhiro, Takasawa, Ken, Minamiya, Yoshihiro, Kobayashi, Kazuma, Okubo, Kenichi, Wakai, Kenji, Shimizu, Atsushi, Yamamoto, Masayuki, Iwasaki, Motoki, Matsuda, Koichi, Inazawa, Johji, Shiraishi, Yuichi, Nishikawa, Hiroyoshi, Murakami, Yoshinori, Kubo, Michiaki, Matsuda, Fumihiko, Kamatani, Yoichiro, Hamamoto, Ryuji, Matsuo, Keitaro, and Kohno, Takashi
- Published
- 2024
8. Age-associated CD4 + T cells with B cell–promoting functions are regulated by ZEB2 in autoimmunity
- Author
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Goto, Manaka, primary, Takahashi, Hideyuki, additional, Yoshida, Ryochi, additional, Itamiya, Takahiro, additional, Nakano, Masahiro, additional, Nagafuchi, Yasuo, additional, Harada, Hiroaki, additional, Shimizu, Toshiaki, additional, Maeda, Meiko, additional, Kubota, Akatsuki, additional, Toda, Tatsushi, additional, Hatano, Hiroaki, additional, Sugimori, Yusuke, additional, Kawahata, Kimito, additional, Yamamoto, Kazuhiko, additional, Shoda, Hirofumi, additional, Ishigaki, Kazuyoshi, additional, Ota, Mineto, additional, Okamura, Tomohisa, additional, and Fujio, Keishi, additional
- Published
- 2024
- Full Text
- View/download PDF
9. Age-associated CD4+ T cells with B cell–promoting functions are regulated by ZEB2 in autoimmunity.
- Author
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Goto, Manaka, Takahashi, Hideyuki, Yoshida, Ryochi, Itamiya, Takahiro, Nakano, Masahiro, Nagafuchi, Yasuo, Harada, Hiroaki, Shimizu, Toshiaki, Maeda, Meiko, Kubota, Akatsuki, Toda, Tatsushi, Hatano, Hiroaki, Sugimori, Yusuke, Kawahata, Kimito, Yamamoto, Kazuhiko, Shoda, Hirofumi, Ishigaki, Kazuyoshi, Ota, Mineto, Okamura, Tomohisa, and Fujio, Keishi
- Subjects
T cells ,B cells ,SYSTEMIC lupus erythematosus ,IMMUNOLOGIC memory ,AUTOIMMUNITY - Abstract
Aging is a significant risk factor for autoimmunity, and many autoimmune diseases tend to onset during adulthood. We conducted an extensive analysis of CD4
+ T cell subsets from 354 patients with autoimmune disease and healthy controls via flow cytometry and bulk RNA sequencing. As a result, we identified a distinct CXCR3mid CD4+ effector memory T cell subset that expands with age, which we designated "age-associated T helper (TH A) cells." TH A cells exhibited both a cytotoxic phenotype and B cell helper functions, and these features were regulated by the transcription factor ZEB2. Consistent with the highly skewed T cell receptor usage of TH A cells, gene expression in TH A cells from patients with systemic lupus erythematosus reflected disease activity and was affected by treatment with a calcineurin inhibitor. Moreover, analysis of single-cell RNA sequencing data revealed that TH A cells infiltrate damaged organs in patients with autoimmune diseases. Together, our characterization of TH A cells may facilitate improved understanding of the relationship between aging and autoimmune diseases. Editor's summary: Pathological CD4+ T cell responses contribute to the development of autoimmunity, but whether their age-related changes affect autoimmune disease susceptibility remains unclear. By analyzing a cohort of 354 patients with autoimmune disease, Goto et al. identified a population of peripheral blood CXCR3mid CD4+ T cells that is expanded during aging and conditions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. These age-associated helper T (TH A) cells promoted antibody production by B cells and were regulated by the transcription factor ZEB2. TH A cell gene signatures correlated with SLE disease activity and were observed in target organs, indicating that TH A cells may represent a therapeutic target for autoimmune diseases. —Claire Olingy [ABSTRACT FROM AUTHOR]- Published
- 2024
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10. Identification of a regulatory pathway governing TRAF1 via an arthritis-associated non-coding variant
- Author
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Wang, Qiang, Martínez-Bonet, Marta, Kim, Taehyeung, Sparks, Jeffrey A., Ishigaki, Kazuyoshi, Chen, Xiaoting, Sudman, Marc, Aguiar, Vitor, Sim, Sangwan, Hernandez, Marcos Chiñas, Chiu, Darren J., Wactor, Alexandra, Wauford, Brian, Marion, Miranda C., Gutierrez-Arcelus, Maria, Bowes, John, Eyre, Stephen, Nordal, Ellen, Prahalad, Sampath, Rygg, Marite, Videm, Vibeke, Raychaudhuri, Soumya, Weirauch, Matthew T., Langefeld, Carl D., Thompson, Susan D., and Nigrovic, Peter A.
- Published
- 2024
- Full Text
- View/download PDF
11. Peripheral blood immunophenotypic diversity in patients with rheumatoid arthritis and its impact on therapeutic responsiveness.
- Author
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Kubo S, Miyazaki Y, Nishino T, Fujita Y, Kono M, Kawashima T, Ishigaki K, Kusaka K, Tanaka H, Ueno M, Satoh-Kanda Y, Inoue Y, Todoroki Y, Miyagawa I, Hanami K, Nakayamada S, and Tanaka Y
- Abstract
Objective: Considering the diverse aetiologies and immunodysregulatory statuses observed in each patient with rheumatoid arthritis (RA), stratification based on peripheral blood immunophenotyping holds the potential to enhance therapeutic responses to molecular targeted therapies, biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs)., Methods: Immunophenotype analysis was conducted on a cohort of over 500 b/tsDMARDs-naïve patients using flow cytometry. Patients with RA were stratified based on their immunophenotypes, and the treatment response to each targeted therapy was evaluated. Validation was performed using an additional cohort of 183 b/tsDMARDs-naïve patients with RA., Results: Patients with RA were stratified into five clusters, two of which exhibited distinct RA phenotypes compared with controls, characterised by significant increases in CD4
+ effector memory T cells re-expressing CD45RA. Notably, the effectiveness of different b/tsDMARDs varied across clusters. The group using promising b/tsDMARDs was labelled as 'expected' whereas the 'non-expected' group comprised those using others. The expected group outperformed the non-expected group with higher 26-week remission rates (39.9% vs 24.6%, p=0.0004) and low disease activity achievement (80.8% vs 60.2%, p<0.0001). Trajectory analysis showed the non-expected group's 26-week disease activity was influenced by Clinical Disease Activity Index at baseline unlike the expected group. Additionally, different molecular targeted therapies influenced the proportions of each immune cell subset variably. To validate, immunophenotyping was performed on a validation cohort. When 183 cases were grouped based on their b/tsDMARDs usage into expected/non-expected groups, the expected group had a higher remission rate (p=0.0021), further confirming the observed trend., Conclusion: Our findings offer valuable insights into the diversity of RA and potential therapeutic strategies grounded in the molecular underpinnings., Competing Interests: Competing interests: SK has received speaking fees from Eli Lilly, GlaxoSmithKline, Bristol Myers, AbbVie, Eisai, Pfizer, AstraZeneca and also research grants from Daiichi Sankyo, AbbVie, Boehringer Ingelheim and Astellas. YM has received consulting fees from AstraZeneca, speaking fees and/or honoraria from Eli Lilly and GlaxoSmithKline. SN has received speaking fees from Bristol Myers, UCB, Astellas, AbbVie, Eisai, Pfizer and Takeda and also research grants from Mitsubishi Tanabe, Novartis and MSD. YTa has received consulting fees, speaking fees and/or honoraria from AbbVie, Daiichi Sankyo, Chugai, Takeda, Mitsubishi Tanabe, Bristol Myers, Astellas, Eisai, Janssen, Pfizer, Asahi Kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD and Santen and also research grants from Mitsubishi Tanabe, Takeda, Chugai, Astellas, Eisai, Taisho Toyama, Kyowa Kirin, AbbVie and Bristol Myers. KI, YF, KK, MK, TN, HT, MU, YS-K, YI, YTo, IM and KH have nothing to declare., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)- Published
- 2024
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12. Unveiling the dynamics of B lymphocytes in systemic lupus erythematosus patients treated with belimumab through longitudinal single-cell RNA sequencing.
- Author
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Bang SY, Suh-Yun Joh C, Itamiya T, Jeong S, Lee JH, Kwon H, Jin H, Jung J, Chung H, Lee BH, Gong JR, Ishigaki K, Fujio K, Bae SC, Je Kim H, and Lee HS
- Abstract
Objectives: Unraveling the mechanisms underlying treatment response for targeted therapeutics in systemic lupus erythematosus (SLE) patients is challenging due to the limited understanding of diverse responses of circulating immune cells, particularly B cells. We investigated B lymphocyte dynamics during anti-BAFF treatment, utilizing longitudinal single-cell transcriptome data., Methods: We conducted single-cell RNA sequencing on PBMCs in four Korean SLE patients before and after belimumab treatment at the following time points: 2 weeks, 1, 3, 6, and 12 months., Results: Analyzing over 73 000 PBMCs, we identified 8 distinct subsets of B cells and plasmablasts and analyzed dynamic changes within these cell subsets: initial declines in naive and transitional B cells followed by an increase at three months, contrasted by an initial increase and subsequent decrease in memory B cells by the third month. Meanwhile, plasmablasts exhibited a consistent decline throughout treatment. B cell activation pathways, specifically in naive and memory B cells, were downregulated during the third and sixth months. These findings were validated at the protein level throughout the first four weeks of treatment using flow cytometry. Comparative analysis with bulk transcriptome data from 22 Japanese SLE patients showed increased NR4A1 expression six months post-belimumab treatment, indicating its role in restricting self-reactive B cells, thereby contributing to the biological responses of anti-BAFF treatment., Conclusion: The observed B cell dynamics provided insights into the immunological mechanisms underlying the therapeutic effects of anti-BAFF in SLE patients. Furthermore, it underscores the need for research in predicting drug responses based on immune profiling., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2024
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13. An atlas of transcribed enhancers across helper T cell diversity for decoding human diseases.
- Author
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Oguchi A, Suzuki A, Komatsu S, Yoshitomi H, Bhagat S, Son R, Bonnal RJP, Kojima S, Koido M, Takeuchi K, Myouzen K, Inoue G, Hirai T, Sano H, Takegami Y, Kanemaru A, Yamaguchi I, Ishikawa Y, Tanaka N, Hirabayashi S, Konishi R, Sekito S, Inoue T, Kere J, Takeda S, Takaori-Kondo A, Endo I, Kawaoka S, Kawaji H, Ishigaki K, Ueno H, Hayashizaki Y, Pagani M, Carninci P, Yanagita M, Parrish N, Terao C, Yamamoto K, and Murakawa Y
- Subjects
- Humans, Cell Differentiation, Chromatin metabolism, Chromatin genetics, Promoter Regions, Genetic, T-Lymphocytes, Helper-Inducer immunology, Single-Cell Gene Expression Analysis, Atlases as Topic, CD4-Positive T-Lymphocytes immunology, Enhancer Elements, Genetic, Transcription Initiation Site, Transcription, Genetic, Genetic Predisposition to Disease
- Abstract
Transcribed enhancer maps can reveal nuclear interactions underpinning each cell type and connect specific cell types to diseases. Using a 5' single-cell RNA sequencing approach, we defined transcription start sites of enhancer RNAs and other classes of coding and noncoding RNAs in human CD4
+ T cells, revealing cellular heterogeneity and differentiation trajectories. Integration of these datasets with single-cell chromatin profiles showed that active enhancers with bidirectional RNA transcription are highly cell type-specific and that disease heritability is strongly enriched in these enhancers. The resulting cell type-resolved multimodal atlas of bidirectionally transcribed enhancers, which we linked with promoters using fine-scale chromatin contact maps, enabled us to systematically interpret genetic variants associated with a range of immune-mediated diseases.- Published
- 2024
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14. Identification of telomere maintenance gene variations related to lung adenocarcinoma risk by genome-wide association and whole genome sequencing analyses.
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Shiraishi K, Takahashi A, Momozawa Y, Daigo Y, Kaneko S, Kawaguchi T, Kunitoh H, Matsumoto S, Horinouchi H, Goto A, Honda T, Shimizu K, Torasawa M, Takayanagi D, Saito M, Saito A, Ohe Y, Watanabe SI, Goto K, Tsuboi M, Tsuchihara K, Takata S, Aoi T, Takano A, Kobayashi M, Miyagi Y, Tanaka K, Suzuki H, Maeda D, Yamaura T, Matsuda M, Shimada Y, Mizuno T, Sakamoto H, Yoshida T, Goto Y, Yoshida T, Yamaji T, Sonobe M, Toyooka S, Yoneda K, Masago K, Tanaka F, Hara M, Fuse N, Nishizuka SS, Motoi N, Sawada N, Nishida Y, Kumada K, Takeuchi K, Tanno K, Yatabe Y, Sunami K, Hishida T, Miyazaki Y, Ito H, Amemiya M, Totsuka H, Nakayama H, Yokose T, Ishigaki K, Nagashima T, Ohtaki Y, Imai K, Takasawa K, Minamiya Y, Kobayashi K, Okubo K, Wakai K, Shimizu A, Yamamoto M, Iwasaki M, Matsuda K, Inazawa J, Shiraishi Y, Nishikawa H, Murakami Y, Kubo M, Matsuda F, Kamatani Y, Hamamoto R, Matsuo K, and Kohno T
- Subjects
- Humans, Genome-Wide Association Study, Whole Genome Sequencing, Telomere genetics, Telomere pathology, Adenocarcinoma of Lung genetics, Lung Neoplasms genetics, Lung Neoplasms pathology
- Published
- 2024
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