システム発生研究部

研究部紹介

遺伝子発現データベースの構築や新規の研究システムの開発、ゲノム情報を利用した解析により、個体発生や細胞分化、組織が構成される際のメカニズムを分子レベルで明らかにし、成育疾患の原因解明へと応用していきます。また、研究成果をもとに疾患モデルマウスを開発していきます。
これまでの研究で、遺伝子が、必要な時期に必要な量を発現しなかった場合に発症する疾患が多数報告されています。正常な胎児の発生や、小児の発育に必要な遺伝子の発現状態と機能を明らかにすることは、成育疾患の原因究明には必要不可欠です。
当部は遺伝子発現の正常な状態を明らかにするとともに、その状態の破綻としての病態の解明を目指します。胎児での解析が可能なマウスをモデルとして用いて、発生学、遺伝学、ゲノム生物学、分子生物学、発生工学に基づいた手法により研究を進めています。現在は主に生殖腺形成（性決定、性分化）、エピジェネティクス、マイクロRNA、ゲノム編集技術について研究しています。

研究内容

1. 新規の遺伝子発現データベースの構築
   胎児の組織が形作られるときの分子メカニズムを理解することは、組織の形成不全や胎児期に由来する成育疾患を理解するために必要不可欠です。そのため、各組織を形作るのに必要な遺伝子の同定を目指して新規遺伝子発現データベースを作製しています。
2. ハイスループット遺伝子発現解析
   胎児の各組織で特異的に発現する遺伝子の発現制御のメカニズムを明らかにするため、多数の遺伝子を細胞に一つずつ強制発現させ、各遺伝子の機能の解析を行っています。この解析のための手法を自動化することにより、ハイスループットな研究が可能になっています。
3. ゲノム科学からの成育疾患の原因解明
   ゲノム配列の中で機能が分かっている部分は一部に過ぎません。機能が不明なゲノムの領域に存在し、成育疾患に関与する配列の同定とゲノムの機能の解析を行っています。この研究により、これまで原因が分からなかった成育疾患の原因の同定や、病態解明を目指しています。
4. 迅速遺伝子破壊マウス作製法による疾患モデルマウスの作製
   近年開発されたゲノム編集法を応用することにより、短時間に遺伝子破壊マウスを作製し、多数の疾患モデルマウスを作ることを目指しています。また、ゲノム編集法を応用した研究手法の開発やさらに高効率な遺伝子破壊マウスの作製法の開発も行っています。
5. 小児難治希少疾患診療の病態解明と治療法開発
   豊富な実績を有する成育医療研究センター病院との緊密な連携を活かし、臨床から生まれた疑問を基礎研究によって解明し、その成果を再び臨床へ還元する、基礎・臨床双方向の研究を進めます。小児難治希少疾患の病態を分子・細胞・個体レベルで明らかにするとともに、新たな診断法や治療法の開発を目指します。具体的には、疾患モデルマウスの作製・解析、基礎研究から得られた知見と臨床情報・臨床検体との統合による病態仮説の検証、さらに希少疾患の遺伝子治療などを用いた新たな治療法の開発に取り組みます。

研究部問い合わせ窓口

システム発生研究部

スタッフ

業績

2026

1. Takeuchi I, Taniguchi K, Arai K, Uchiyama T, Terao M, Hori A, Kawai T, Yoshioka T, Kyodo R, Shimizu H, Fujita S, Motomura K, Okazaki Y, Ishikawa T, Ogura M, Hayashi K, Matsumoto K, Takada S: Onodera M, Morita H, Hata K. Inflammatory bowel disease in a young female patient with a novel de novo TRAF3 frameshift variant responsive to ustekinumab: a case report. Intestinal Research, 24:182-188 (2026).
2. Yamanaka H, Okamura K: Exploring deep learning and data requirements through image classification of Erigeron annuus and Erigeron philadelphicus. BMC Res. Notes, 16;19(1):127 (2026).
3. Hu X, Shui Y, Fan Y, Takada S, Terao M, Shindo M:　Que　W, Fujino　M, Guo W, Li X. Phenotypically and functionally unique CD86 expression CD8 T cell subset shapes immune regulation in the tumor microenvironment. Journal of Advanced Research, 5:S2090-1232(26)00285-7 (2026).
4. Tsuchiya I, Tsuji-Hosokawa A, Furuhashi S, Sugiyama K, Ogawa Y, Oishi A, Terao M, Takada S: Strain-dependent functional variation of a sex specific Sox9 enhancer. Genes to Cells, 31(4):e70131 (2026).
5. Ito M, Katoh M, Kubota M, Yamasaki M, Zhang Y, Komuro J, Tsukihashi A, Yamada S, Ko T, Katagiri M, Abe R, Inoue S, Hiruma T, Nishijo D, Dai Z, Morita H, Toyoda M, Takada S, Ikeuchi M, Matsuura K, Umezawa A, Aburatani H, Onoue K, Nomura S, Takeda N, Komuro I. Vitamin D Pathway Activation Reduces Cardiomyocyte DNA Damage and Improves Cardiac Contractility in Preclinical Models. JACC: Advances, 2:103199 (2026).
6. Konishi A, Tachibana M, Oto Y, Kashimada K, Ishii T, Aoki Y, Muroya K, Takahashi Y, Kurosawa K, Ogata T, Kawai M: Health-Related Quality of Life and Its Related Factors in Adolescents and Adults With Prader-Willi Syndrome in Japan. Am J Med Genet A, doi: 10.1002/ajmg.a.70222 (2026).
7. Koga N, Katoh-Fukui Y, Fukui S, Kashimada K, Fukami M: GATA4 Single-Amino Acid, Deletion in a Male Patient With Congenital Heart Defects, Differences of Sex, Development, and Diaphragmatic Hernia. Clin Genet, 110(3):374-378 (2026).
8. Nishimoto Y, Fukui S, Shioda S, Kurosawa K, Uematsu S, Matsumoto S, Kashimada K: Repeated and Severe Salt-Wasting Crisis in a Case of Type 1 Pseudohypoaldosteronism. Pediatr Int, 68(1):e70445 (2026).
9. Terashita S, Nagamori M, Naiki Y, Sugiura A, Ujita N, Kashimada K, Imai C: Clinical utility of TRAb reduction in predicting remission in pediatric Graves' disease. Clin Pediatr Endocrinol, 35(2):161-167 (2026).
10. Iemura R, Suzuki Y, Gau M, Orimoto R, Yamano H, Nakatani H, Kirino S, Saito Y, Adachi E, Tsuji-Hosokawa A, Kashimada K, Takasawa K., Gonadotropin Suppression During Mini-Puberty as an Early Biomarker of Classic 21-Hydroxylase Deficiency., Endocrinol Diabetes Metab. 9(5):e70317. doi: 10.1002/edm2.70317(2026).
11. Tanimoto E, Kashimada K, Matsuura B, Yamaguchi H, Kurajoh M, Segawa T, Ohba K, Abe Y, Wada Y, Kanno J, Oda Y, Tajima T, Shibata H, Hasegawa T. Clinical features of hereditary adrenocortical unresponsiveness to adrenocorticotropin (HAUA) in Japan: from a nationwide questionnaire based survey. Endocr J. doi: 10.1507/endocrj.EJ26-0099(2026).
12. Mauras N, Boettcher C, Højby M, Soltysik K, Jorge AAL, Kashimada K, Linglart A, Luo X, Murray PG, Backeljauw P. Once-weekly somapacitan enhances linear growth in girls with Turner syndrome: a randomized controlled phase 3 study. J Clin Endocrinol Metab.:dgag309. doi: 10.1210/clinem/dgag309(2026).
13. Nakano Y, Suzuki H, Kuroda Y, Yoshihashi H, Okamoto N, Kondo A, Kosaki R, Kashimada K, Kurihara T, Thong MK, Tae SK, Rifhan M, Enokizono T, Suzumura H, Yoshida T, Kosugi S, Mizuno S, Inaba M, Nakamura N, Matsufuji M, Ogawa E, Yagi H, Yamada M, Qian E, Nakato D, Takenouchi T, Kosaki K, Miya F. Whole-genome discovery of pathogenic snRNA variants and efficient extended-exome screening. iScience. 29(8):116814. doi: 10.1016/j.isci.2026.116814(2026).
14. Wada Y, Furujo M, Kashimada K, Hamazaki T, Nyuzuki H, Ichimoto K, Kakiuchi T, Matsumoto S, Watanabe Y, Ono C, Shimizu T, Furukawa H, Nakamura K. Long-Term Efficacy and Safety of Glycerol Phenylbutyrate in Japanese Patients With Urea Cycle Disorders: Results From a Phase 3 Switch-Over and 12-Month Extension Study. JIMD Rep. 67(4):e70082. doi: 10.1002/jmd2.70082. eCollection (2026).

2025

1. Ogawa Y, Tsuchiya I, Yanai S, Baba T, Morohashi K-I, Sasaki T, Sasaki J, Terao M, Tsuji-Hosokawa A, Takada S: GATA4 binding to the Sox9 enhancer mXYSRa/Enh13 is critical for testis differentiation in mouse. Communications Biology, 8(1):81 (2025).
2. Ogawa Y, Tsuchiya I, Yanai S, Baba T, Morohashi K-I, Sasaki T, Sasaki J, Terao M, Tsuji-Hosokawa A, Takada S: Author Correction: GATA4 binding to the Sox9 enhancer mXYSRa/Enh13 is critical for testis differentiation in mouse. Communications Biology, 8:199 (2025).
3. Tsuji-Hosokawa A, Tsuchiya I, Shimizu K, Terao M, Yasuhara M, Miyamoto N, Kikuchi S, Ogawa Y, Nakamura K, Matsubara Y, Takada S: Genetically humanized phenylketonuria mouse model as a testing tool for human genome editing in fertilized eggs. Journal of Inherited Metabolic Disease, 48:e12803 (2025).
4. Taniguchi K, Hasegawa F, Okazaki Y, Hori A, Ogata-Kawata H, Aoto S, Migita O, Kawai T, Nakabayashi K, Okamura K, Fukui K, Wada S, Ozawa K, Ito Y, Sago H, Hata K: Approaches to evaluate whole exome sequencing data that incorporate genetic intolerance scores for congenital anomalies, including intronic regions adjacent to exons. Mol. Genet. Genomic Med, 13, e70092 (2025).
5. Shibata M, Umezawa A, Aoto S, Okamura K, Nasu M, Mizuno R, Oya M, Yura K, Mikami S: Applicability of the regression approach for histological multi-class grading in clear cell renal cell carcinoma. Regen. Ther, 28, 431-437 (2025).
6. Hara S, Muramatsu A, Terao M, Takada S: Identification of maternal allele sequences of IG-DMR that are essential for neonatal viability. PLoS One, 20(5):e0324882 (2025).
7. Ko T, Nishijo D, Tsuji-Hosokawa A, Tsuchiya I, Nomura S, Zhang B, Jiang Y, Fujimori K, Hiruma T, Abe R, Jimba T, Inoue S, Dai Z, Katoh M, Katagiri M, Ito M, Morita H, *Takada S, Takeda N, Umezawa A, Komuro I: Correction of the murine model of congenital heart disease associated with the Nkx2-5 mutation using prime editing. Circulation: Genomic and Precision Medicine, 18:e005194 (2025).
8. Fujita S, Kabashima S, Yanagi K, Toyokuni K, Yoshida K, Miyaji Y, Takada S, Motomura K, Tamari M, Nakazaki H, Hayashi Y, Nagano N, Uchiyama T, Oishi K, Yokoya S, Yoshioka T, Tanase-Nakao K, Yamamoto-Hanada K, Fukuie T, Horikawa R, Saito H, Matsubara Y, Ohya Y, Kaname T, Matsumoto K, Morita H; JAK1 gain-of-function variant causes alopecia areata, atopic dermatitis, and autoimmune thyroid disease. Journal of Allergy and Clinical Immunology, 156(6):1769-1771 (2025).
9. Miyai M, Tanaka-Yachi R, Aizawa K, Okamura K, Kusuhara H, Akutsu H, Nakamura K. Removing extracellular matrix from the cell surface prior to seeding enhances the adhesion of primary human hepatocytes to the culture vessel. Genes Cells, 30, e70059 (2025).

2024

1. Amano N, Narumi S, Aizu K, Miyazawa M, Okamura K, Ohashi H, Katsumata N, Ishii T, Hasegawa T: Single-exon deletions of ZNRF3 exon 2 cause congenital adrenal hypoplasia. Journal of Clinical Endocrinology & Metabolism, 20;109(3):641-648 (2024).
2. Kawai T, Kinoshita S, Takayama Y, Onishi E, Kamura H, Kojima K, Kikuchi H, Terao M, Sugawara T, Migita O, Kagami M, Yamaguchi Y, Wakui K, Ohashi H, Shimizu K, Mizuno S, Okamoto N, Fukushima Y, Takada F, Kosaki K, Takada S, Akutsu H, Ura K, Nakabayashi K, Hata K: Loss-of-function in NSD2 causes DNA methylation signature similar to that in Wolf-Hirschhorn syndrome. Genetics in Medicine Open, 14:2:101838 (2024).
3. Kinoshita S, Kojima K, Ohnishi E, Takayama Y, Kikuchi H, Takada S, Nakabayashi K, Kawai T, Hata K: Loss of NSD2 causes dysregulation of synaptic genes and altered H3K36 dimethylation in mice. Frontiers in Genetics, 15:1308234 (2024).
4. Abe T, Kanno SI, Niihori T, Terao M, Takada S, Aoki Y: LZTR1 deficiency exerts high metastatic potential by enhancing sensitivity to EMT induction and controlling KLHL12-mediated collagen secretion. Cell Death & Disease, 14:556 (2023).
5. Yoshida T, Yokoi T, Tanaka T, Matsuzaka E, Saida Y, Nishina S, Takada S, Shimizu S, Azuma N: Modeling of retina and optic nerve ischemia-reperfusion injury through hypoxia-reoxygenation in human induced pluripotent stem cell-derived retinal ganglion cells. Cells,13:130 (2024).
6. Kawano T, Okamura K, Shinchi H, Ueda K, Nomura T, Shiba K: Differentiation of large extracellular vesicles in oral fluid: combined protocol of small force centrifugation and sedimentation pattern analysis. Journal of Extracellular Biology, 3:e143 (2024).
7. Shindo M, Terao M, Takada S, Ichinose M, Matsuzaka E, Yokoi T, Azuma N, Mizuno S, Tsumura H: Establishment and visual analysis of CBA/J-Pde6bY347Y/Y347X and C3H/HeJ-Pde6bY347Y/Y347X mice. Experimental Animals, 73(2):203-210 (2024).
8. Matsubara K, Ohgami Y, Okamura K, Aoto S, Fukami M, Shimada Y: Machine learning trial to detect sex differences in simple sticker arts of 1606 preschool children. Minerva Pediatr, 76:343-349 (2024).
9. Hattori A, Seki A, Inaba N, Nakabayashi K, Takeda K, Tatsusmi K, Naiki Y, Nakamura A, Ishiwata K,Matsumoto K, Nasu M, Okamura K, Michigami T, Katoh-Fukui Y, Umezawa A, Ogata T, Kagami M,Fukami M: Expression levels and DNA methylation profiles of the growth gene SHOX in cartilage tissues and chondrocytes. Sci. Rep, 14:8069 (2024).
10. M Morita-Nakagawa M, Okamura K, Nakabayashi K, Inanaga Y, Shimizu S, Guo WZ, Fujino M, Li XK: Supervised machine learning of outbred mouse genotypes to predict hepatic immunological tolerance of individuals. Sci. Rep, 17;14(1):24399 (2024)
11. Ito M, Katoh M, Sassa T, Ko T, Fujita K, Yamada S, Miura K, Toyoda M, Takada S, Tobita T, Katagiri M, Kubota M, Yamada T, Hatsuse S, Morita H, Ikeuchi M, Matsuura K, Umezawa A, Nomura S, Aburatani H, Komuro I: LMNA p.Q353R mutation causes dilated cardiomyopathy through impaired vitamin D signaling. Circulation, 17;150(12):971-974 (2024).
12. Abe T, Morisaki K, Niihori T, Terao M, Takada S, Aoki Y: Dysregulation of RAS proteostasis by autosomal-dominant LZTR1 mutation induces Noonan syndrome-like phenotypes in mice, JCI Insight, 22;9(22):e182382 (2024).
13. Uchida N, Ishii T, Amano N, Takada S, Kobayashi K, Murakami T, Narumi S, Hasegawa T: Znrf3 exon 2 deletion mice do not recapitulate congenital adrenal hypoplasia. J Mol Endocrinol, 73:e240015 (2024).

2023

1. Ogawa Y, Terao M, Tsuji-Hosokawa A, Tsuchiya I, Hasegawa M, Takada S: SOX9 and SRY binding sites on mouse mXYSRa/Enh13 enhancer redundantly regulate Sox9 expression to varying degrees. Human Molecular Genetics, 1;32(1):55-64 (2023).
2. Azuma N, Yokoi T, Tanaka T, Matsuzaka E, Saida Y, Nishina S, Terao M, Takada S, Fukami M, Okamura K, Maehara K, Yamasaki T, Hirayama J, Nishina H, Handa H, Yamaguchi Y: Integrator complex subunit 15 controls mRNA splicing and is critical for eye development. Human Molecular Genetics, 5;32(12):2032-2045 (2023).
3. Richard Albert J, Kobayashi T, Inoue A, Monteagudo‐Sánchez A, Kumamoto S, Takashima T, Miura A, Oikawa M, Miura F, Takada S, Hirabayashi M, Korthauer K, Kurimoto K: Greenberg MVC, Lorincz M, Kobayashi K. Conservation and divergence of canonical and non-canonical imprinting in murids. Genome Biology, 24:48 (2023).
4. Mashima R, Ohira M, Okuyama T, Onodera M, Takada S: A novel mucopolysaccharidosis type II mouse model with an iduronate-2-sulfatase-P88L mutation. Scientific Reports, 13(1):7865 (2023).
5. Yamada S, Ko T, Ito M, Sassa T, Nomura S, Okuma H, Sato M, Imasaki T, Kikkawa S, Zhang B, Yamada T, Seki Y, Fujita K, Katoh M, Kubota M, Hatsuse S, Katagiri M, Hayashi H, Hamano M, Takeda N, Morita H, Takada S, Toyoda M, Uchiyama M, Ikeuchi M, Toyooka K, Umezawa A, Yamanishi Y, Nitta R, Aburatani H, Komuro I: TEAD1 trapping by the Q353R-Lamin A/C causes dilated cardiomyopathy. Science Advances, 9(15):eade7047 (2023).
6. Katoh-Fukui Y, Hattori A, Zhang R, Terao M, Takada S, Nakabayashi K, Hata K, Yamada Y, Matsuura N, Fukami M: Chromosomal microdeletion leading to pituitary gigantism through hormone-gene overexpression. Human Molecular Genetics, 4;32(14):2318-2325 (2023).
7. Yoshida M, Nakabayashi K, Yang W, Sato-Otsubo A, Tsujimoto SI, Ogata-Kawata H, Kawai T, Ishiwata K, Sakamoto M, Okamura K, Yoshida K, Shirai R, Osumi T, Kiyotani C, Shioda Y, Terashima K, Ishimaru S, Yuza Y, Takagi M, Arakawa Y, Imamura T, Hasegawa D, Inoue A, Yoshioka T, Ito S, Tomizawa D, Koh K, Matsumoto K, Kiyokawa N, Ogawa S, Manabe A, Niwa A, Hata K, Yang JJ, Kato M: Prevalence of pathogenic variants in cancer-predisposing genes in second cancer after childhood solid cancers. Cancer Medicine, 12, 11264-11273 (2023).
8. Abe T, Kanno S, Niihori T, Terao M, Takada S, Aoki Y: LZTR1 deficiency exerts high metastatic potential by enhancing sensitivity to EMT induction and controlling KLHL12-mediated collagen secretion. Cell Death & Disease, 25;14(8):556 (2023).
9. Uchiyama T, Kawai T, Nakabayashi K, Nakazawa Y, Goto F, Okamura K, Nishimura T, Kato K, Watanabe N, Miura A, Yasuda T, Ando Y, Minegishi T, Edasawa K, Shimura M, Akiba Y, Sato-Otsubo A, Mizukami T, Kato M, Akashi K, Nunoi H, Onodera M: Myelodysplasia after clonal hematopoiesis with APOBEC3-mediated CYBB inactivation in retroviral gene therapy for X-CGD. Molecular Therapy, 6;31(12):3424-3440 (2023).
10. Yamazaki N, Ohira M, Takada S, Ohtake A, Onodera M, Nakanishi M, Okuyama T, Mashima R: Enhanced osteoblastic differentiation of parietal bone in a novel murine model of mucopolysaccharidosis type II. Molecular Genetics and Metabolism Reports, 11:37:101021 (2023).
11. Takeuchi I, Yanagi K, Takada S, Uchiyama T, Igarashi T, Motomura K, Hayashi Y, Nagano N, Matsuoka R, Sugiyama H, Yoshioka T, Saito H, Kawai T, Miyaji Y, Inuzuka Y, Matsubara Y, Ohya Y, Shimizu T, Matsumoto K, Arai K, Nomura I, Kaname T, Morita H: STAT6 gain-of-function variant exacerbates multiple allergic symptoms. The Journal of Allergy and Clinical Immunology, 151(5):1402-1409.e6, (2023).

2022

1. Nakagawa R, Takasawa K, Tsuji-Hosokawa A, Kawaji H, 
Murakawa Y, Takada S, Mikami M, Narumi S, FukamiM, Sreenivasan R, Maruyama T, Tucker E, Zhao L, Bowles J, 
Sinclair A, Koopman P, Hayashizaki Y, Morio T, Kashimada K: Two ovarian candidate enhancers, identified by time series enhancer RNA analyses, harbor rare genetic variations identified in ovarian insufficiency. Human Molecular Genetics, 7;31(13):2223-2235 (2022).
2. Naiki Y, Miyado M, Shindo M, Horikawa R, Hasegawa Y, Katsumata N, Takada S, Akutsu H, Onodeara M, Maki Fukami M: AAV-mediated gene therapy for patients' fibroblasts, iPS cells, and a mouse model of congenital adrenal hyperplasia. Human Gene Therapy, 33(15-16):801-809 (2022).
3. Inoue M, Baba T, Takahashi F, Terao M, Miyabayashi K, Shima Y, Saito D, Sugiura K, Miura T, Takada S, Suyama M, Ohkawa Y, Morohashi K-I: Tmsb10 triggers fetal Leydig differentiation by suppressing the RAS/ERK pathway. Communications Biology, 15;5(1):974 (2022).
4. Terao M, Ogawa Y, Takada S, Kajitani R, Okuno M, Mochimaru Y, Matsuoka K, Itoh T, Toyoda A, Kono T, Jogahara T, Mizushima S, Kuroiwa A: Turnover of mammal sex chromosomes in the Sry-deficient Amami spiny rat is due to male-specific upregulation of Sox9, Proceedings of the National Academy of Sciences of the United States of America, 6;119(49):e2211574119 (2022).
5. Akiba K, Hasegawa Y, Katoh-Fukui Y, Terao M, Takada S, Hasegawa T, Fukami M, Narumi S: POU1F1/Pou1f1 c.143-83A>G variant disrupts the branch site in pre-mRNA and leads dwarfism. Endocrinology, 19;164(2):bqac198 (2022).
6. Uryu H, Migita O, Ozawa M, Kamijo C, Aoto S, Okamura K, Hasegawa F, Okuyama T, Kosuga M, Hata K: Automated urinary sediment detection for Fabry disease using deep-learning algorithmsMolecular Genetics and Metabolism Reports, 33, 100921 (2022).