1: New Technology for Direct Induction of Neurons from Blood Cells - Development of a Partial Reprogramming Method Using the NEUROD1 Gene - / 2: Brain Imaging and Post-mortem Brain Data Demonstrate Involvement of Tau Protein in Mood Disorders with Middle-age and Late-life Onset
Science of the Month - July 2025
1: New Technology for Direct Induction of Neurons from Blood Cells - Development of a Partial Reprogramming Method Using the NEUROD1 Gene -
Proc Natl Acad Sci USA.
Yoichi Saito, Mitsuru Ishikawa, Mahito Ohkuma, Jonathan Moody, Yo Mabuchi, Tsukasa Sanosaka, Yoshinari Ando, Takayuki Yamashita, Chung Chau Hon, Jay W Shin, Wado Akamatsu, Hideyuki Okano
We have developed a new technology to convert blood cells into neurons in a culture dish by introducing a specific set of genes. This study utilizes a method called partial reprogramming, in which the bHLH-type transcription factor NEUROD1, involved in neural differentiation, and four genes used in the establishment of iPS cells (OCT3/4, SOX2, KLF4, c-MYC) are introduced into peripheral blood T cells. As a result, it has become possible to produce glutamatergic neurons in a short period of approximately 20 days. Previously known direct neuron induction methods mainly used skin fibroblasts, which required skin incision and suturing for cell collection. Since this technology can produce large quantities of functional neurons in a short period while significantly reducing donor invasiveness, it is expected to contribute to increasing throughput in the development of treatments for neurological diseases.
(Yoichi Saito, Hideyuki Okano, Keio University Regenerative Medicine Research Center (KRM))
2: Brain Imaging and Post-mortem Brain Data Demonstrate Involvement of Tau Protein in Mood Disorders with Middle-age and Late-life Onset
Alzheimers Dement.
Shin Kurose, Sho Moriguchi, Manabu Kubota, Kenji Tagai, Yuki Momota, Masanori Ichihashi, Yasunori Sano, Hironobu Endo, Kosei Hirata, Yuko Kataoka, Ryoji Goto, Yuki Mashima, Yasuharu Yamamoto, Hisaomi Suzuki, Shinichiro Nakajima, Masashi Mizutani, Terunori Sano, Kazunori Kawamura, Ming-Rong Zhang, Harutsugu Tatebe, Takahiko Tokuda, Mitsumoto Onaya, Masaru Mimura, Naruhiko Sahara, Hidehiko Takahashi, Hiroyuki Uchida, Masaki Takao, Jeffrey H Meyer, Makoto Higuchi, Keisuke Takahata
Recent epidemiological studies have suggested that mood disorders developing in middle and old age may be a precursor to dementia. While the abnormal accumulation of tau and amyloid-β is involved in many types of dementia, how these affect mood disorders has remained unclear. In this study, we investigated tau lesions in patients with depression and bipolar disorder that developed after age 40 using the PET tracer florzolotau (18F), which can detect tau pathology. The results showed that even after accounting for gender, age, and general cognitive function, the patient group had a tau lesion positivity rate approximately 4.8 times higher than healthy individuals of the same age. Furthermore, an analysis using data from the National Center of Neurology and Psychiatry Brain Bank confirmed that patients who first experienced depressive or manic states after age 40 had a high proportion of tau lesions, and that mood symptoms preceded cognitive impairment by an average of 7 years. These findings confirm in vivo that tau lesions are already accumulating before the onset of dementia in some patients with middle-age and late-life onset mood disorders, and this was further supported by post-mortem brain data. This is an important finding indicating the need for diagnosis and treatment based on objective biomarkers using molecular imaging in the clinical care of middle-age and late-life onset mood disorders.
(Shin Kurose, Keisuke Takahata, Department of Neuropsychiatry)
Other Published Papers
1: An organoid library unveils subtype-specific IGF-1 dependency via a YAP-AP1 axis in human small cell lung cancer.
Nature Cancer.
Fukushima T, Togasaki K, Hamamoto J, Emoto K, Ebisudani T, Mitsuishi A, Sugihara K, Shinozaki T, Okada M, Saito A, Takaoka H, Ito F, Shigematsu L, Ohta Y, Takahashi S, Matano M, Kurebayashi Y, Ohgino K, Sato T, Kawada I, Asakura K, Hishida T, Asamura H, Ikemura S, Terai H, Soejima K, Oda M, Fujii M, Fukunaga K, Yasuda H, Sato T.