Review
Cell & Tissue Engineering
Chunmeng Yao, Ruqiang Yao, Haining Luo, Ling Shuai
Summary: This review describes in vitro germline specification studies, focusing on the reconstitution of PGCs, meiosis, signaling pathways, and factors involved in these processes.
STEM CELL RESEARCH & THERAPY
(2022)
Review
Endocrinology & Metabolism
Ila Tewari Jasra, Nerea Cuesta-Gomez, Kevin Verhoeff, Braulio A. Marfil-Garza, Nidheesh Dadheech, A. M. James Shapiro
Summary: This review summarizes the roles and mechanisms of mitochondria in somatic cell reprogramming to iPSCs and the metabolic shift associated with directed differentiation into pancreatic beta-like cells.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Deogil Kim, Byung-Hyun Cha, Jinsung Ahn, Yoshie Arai, Bogyu Choi, Soo-Hong Lee
Summary: Understanding the biophysical relationships between stem cells and applied biomaterials is crucial in controlling stem cell functions. This study highlights the significant role of 3D microenvironment, particularly methacrylated hyaluronic acid (HA) hydrogel, in improving cellular reprogramming into iPSCs. The incorporation of cues from the 3D microenvironment accelerates the reprogramming process, offering potential advantages for translational applications.
ADVANCED FUNCTIONAL MATERIALS
(2021)
Article
Multidisciplinary Sciences
Jingyang Guan, Guan Wang, Jinlin Wang, Zhengyuan Zhang, Yao Fu, Lin Cheng, Gaofan Meng, Yulin Lyu, Jialiang Zhu, Yanqin Li, Yanglu Wang, Shijia Liuyang, Bei Liu, Zirun Yang, Huanjing He, Xinxing Zhong, Qijing Chen, Xu Zhang, Shicheng Sun, Weifeng Lai, Yan Shi, Lulu Liu, Lipeng Wang, Cheng Li, Shichun Lu, Hongkui Deng
Summary: This study demonstrates the chemical reprogramming of human somatic cells to human chemically induced pluripotent stem cells, which exhibit key features of embryonic stem cells. The induction of an intermediate plastic state and inhibition of the JNK pathway are crucial for successful chemical reprogramming.
Article
Biology
Praveen Kumar Guttula, Pedro T. Monteiro, Mukesh Kumar Gupta
Summary: This study predicted and modeled synergistic microRNA regulatory networks, identifying the crucial roles of miR-200/429/141 family in controlling pluripotency and reprogramming, and the essential functions of miR-20/106/17 family in maintaining unipotent cells. The logical modeling demonstrated that synergistic miRNAs regulate MET gene dynamics during reprogramming, which was confirmed by perturbation analysis.
Review
Immunology
Niclas Flosdorf, Martin Zenke
Summary: Novel methods of generating dendritic cells (DC) through reprogramming somatic cells have opened up exciting avenues for research and clinical applications. Induced pluripotent stem cells (iPS cells) and direct reprogramming of cells can both be used to generate DC.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Cell & Tissue Engineering
Kazuto Kimura, Masaya Tsukamoto, Miyuu Tanaka, Mitsuru Kuwamura, Manami Ohtaka, Ken Nishimura, Mahito Nakanishi, Kikuya Sugiura, Shingo Hatoya
Summary: This study developed an efficient strategy to generate ciPSCs from canine PBMCs by adding small-molecule compounds in the medium. The generated ciPSCs demonstrated pluripotency characteristics, maintained a normal karyotype, and could differentiate into cells from three germ layers. This method provides a potential tool for disease modeling and regenerative medicine in veterinary field.
STEM CELLS AND DEVELOPMENT
(2021)
Article
Cell Biology
Olga A. Krasnova, Karina A. Kulakova, Julia V. Sopova, Evgenyi Y. Smirnov, Sergey A. Silonov, Ekaterina V. Lomert, Olga A. Bystrova, Marina G. Martynova, Irina E. Neganova
Summary: G-protein-coupled receptors (GPCRs) are the largest family of cell surface receptors and play important roles in diverse developmental processes. However, their role in pluripotency maintenance and acquisition during reprogramming towards hiPSCs has been overlooked. Through RNA interference screening, adhesion GPCR GPR123 was identified as a potential reprogramming effector. Suppression of GPR123 leads to loss of pluripotency and differentiation in hPSCs, suggesting its essential role in maintaining and acquiring pluripotency.
Article
Cell & Tissue Engineering
Sandhya Sriram, Nam-Young Kang, Subha Subramanian, Tannistha Nandi, Samydurai Sudhagar, Qiaorui Xing, Gerine Jin-Ling Tong, Allen Kuan-Liang Chen, Thekkeparambil Chandrabose Srijaya, Patrick Tan, Yuin-Han Loh, Young-Tae Chang, Shigeki Sugii
Summary: In this study, a novel BODIPY-derived fluorescent probe, BDL-E5, was identified to detect live human iPS cells at the early reprogramming stage, enabling early identification of reprogramming cells and improving the efficiency of iPS cell generation. RNA sequencing analysis revealed early reprogramming gene expression patterns, particularly involving CREB1, which was found to significantly impact reprogramming efficiency when overexpressed or knocked down. Overall, BDL-E5 provides a valuable tool for studying the early reprogramming pathway and enhancing the production of human iPS cells for clinical applications.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Cell & Tissue Engineering
Siying Liu, Shuang Zhao, Chuanyu Zhang, Chenglei Tian, Dan Wang, Huaxin Yu, Zongjin Li, Lin Liu, Na Liu
Summary: Dppa3 is crucial for chimera formation and germline competence in mouse pluripotent stem cells (PSCs), acting through regulation of DNA methylation and maintaining DNA hypomethylation balance. PSCs with high Dppa3 expression exhibit increased germline competence, while Dppa3 deficiency reduces chimera formation and germline transmission capacity.
STEM CELL REVIEWS AND REPORTS
(2023)
Article
Medicine, General & Internal
Chao-Yu Liu, Ming-Cheng Lee, Heng-Fu Lin, Yi-Ying Lin, Wei-Yi Lai, Yueh Chien, Teh-Ia Huo, Wen-Liang Lo, Yuan-Tzu Lan, Yi-Wei Chen, Pin- Huang, Yong-Yang Liu, Meng-Yin Yang
Summary: This study utilized nanodiamond as a gene delivery vehicle to carry microRNA (miR-181a) into induced pluripotent stem cells (iPS) to promote cardiomyocyte-lineage differentiation. The miR-181a targeted Hox-A11, leading to elevated MyoD expression and enhanced cardiomyocyte differentiation.
JOURNAL OF THE CHINESE MEDICAL ASSOCIATION
(2021)
Article
Biochemistry & Molecular Biology
Jiawei Xu, Yimin Shu, Guidong Yao, Yu Zhang, Wenbin Niu, Yile Zhang, Xueshan Ma, Haixia Jin, Fuli Zhang, Senlin Shi, Yang Wang, Wenyan Song, Shanjun Dai, Luyao Cheng, Xiangyang Zhang, Wei Xie, Aaron J. Hsueh, Yingpu Sun
Summary: Research on the production of uniparental human embryos has led to the successful generation of human diploid AG embryos capable of developing into blastocysts with an identifiable inner cell mass and trophectoderm, as well as GG embryos. DNA methylome analysis showed differences in methylation patterns between GG and AG embryos, with GG blastocysts partially retaining the oocyte transcription-dependent methylation pattern while AG blastocysts exhibited more extensive demethylation. The study also identified new candidate imprinted differentially methylated regions (DMRs) in the embryos.
Article
Cell & Tissue Engineering
Ana Belen Alvarez-Palomo, Jordi Requena-Osete, Raul Delgado-Morales, Victoria Moreno-Manzano, Carme Grau-Bove, Agueda M. Tejera, Manel Juan Otero, Carme Barrot, Irene Santos-Barriopedro, Alejandro Vaquero, Jovita Mezquita-Pla, Sebastian Moran, Carlos Hobeich Naya, Iris Garcia-Martinez, Francisco Vidal Perez, Maria A. Blasco, Manel Esteller, Michael J. Edel
Summary: The study demonstrates that utilizing synthetic mRNA transfection of CYCLIN D1 during reprogramming repairs DNA and significantly improves the genetic stability of human iPSC. This method reduces various genetic instabilities, decreases DNA damage, promotes correct protein expression, and reduces single-nucleotide polymorphism changes per chromosome.
Article
Cell Biology
Xiugong Gao, Rong Li, Robert L. Sprando, Jeffrey J. Yourick
Summary: The study found that exposure to different concentrations of silver nanoparticles induced gene expression changes in iPSC-HLCs, mainly involving oxidative stress and cellular protective responses. Functional analysis revealed that differentially expressed genes were primarily involved in metabolism, stress response, and cell organization and biogenesis.
CELL BIOLOGY AND TOXICOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Hyun Kyu Kim, Tae Won Ha, Man Ryul Lee
Summary: Cells are the basic units of organisms, with over 30 trillion cells generated from a single-cell fertilized egg through division and differentiation. Establishing the Human Cell Atlas aims to understand the mechanisms underlying diseases and cellular activities.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Daiki Karigane, Miho Haraguchi, Noriko Toyama-Sorimachi, Emi K. Nishimura, Keiyo Takubo
Summary: Thymic dendritic cells (DCs) play a pivotal role in immune tolerance by regulating negative selection of autoreactive T cells in the thymus. This study reveals that the transcription factor Mitf is involved in the regulation of DC homing to the thymus and maintenance of thymic DC population.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Hematology
Shinya Fujita, Takayuki Morikawa, Shinpei Tamaki, Maiko Sezaki, Hitoshi Takizawa, Shinichiro Okamoto, Keisuke Kataoka, Keiyo Takubo
Summary: This study characterizes the distribution of sympathetic and nociceptive nerves in bone marrow using three-dimensional quantitative microscopy. It reveals that sympathetic and nociceptive nerves are the major fibers in bone marrow and are mostly associated with arteries and arterioles.
EXPERIMENTAL HEMATOLOGY
(2022)
Article
Biology
Yuji Takihara, Takumi Higaki, Tomomasa Yokomizo, Terumasa Umemoto, Kazunori Ariyoshi, Michihiro Hashimoto, Maiko Sezaki, Hitoshi Takizawa, Toshihiro Inoue, Toshio Suda, Hidenobu Mizuno
Summary: This study developed an intravital imaging method to observe the migration dynamics of hematopoietic stem cells (HSCs) during bone marrow formation. Neonatal HSCs migrate from outside to inside the tibia via the blood vessels that penetrate the bone, and settle on the blood vessel wall in the bone marrow.
COMMUNICATIONS BIOLOGY
(2022)
Article
Immunology
Chong Yang, Rui Yokomori, Lee Hui Chua, Shi Hao Tan, Darren Qiancheng Tan, Kenichi Miharada, Takaomi Sanda, Toshio Suda
Summary: In this study, we demonstrated the functional importance of intercellular mitochondria transfer in mediating the recovery of recipient erythroblasts from anemic stress. We found that CD47 marked a subset of metabolically active erythroid populations with higher abundance of mitochondria transfer. By infusing EBI macrophages into mice subjected to different modes of anemic stress, we observed the occurrence of mitochondria transfer events from the infused EBI macrophages to early stages of erythroblasts, leading to enhanced erythroid recovery. Single-cell RNA-sequencing analysis on erythroblasts receiving exogenous mitochondria revealed a subset of highly proliferative and metabolically active erythroid populations marked by high expression of CD47. Blocking CD47 or Sirp alpha resulted in a decline in both the occurrence of mitochondria transfer events and their mediated erythroid recovery. These findings suggest that mitochondria transfer plays a significant role in enhancing erythroid recovery from stress through the alteration of bioenergetic profiles via CD47-Sirp alpha interaction in the early stages of erythroblasts.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Review
Cell Biology
Hiroshi Kobayashi, Shintaro Watanuki, Keiyo Takubo
Summary: This review article introduces the methods, characteristics, and regulatory mechanisms of metabolic analysis of tissue stem/progenitor cells. Studying these aspects contributes to the advancement of stem cell biology and engineering, as well as the establishment of therapeutic approaches.
Meeting Abstract
Hematology
Shinya Fujita, Takayuki Morikawa, Keisuke Kataoka, Keiyo Takubo
Article
Medicine, General & Internal
Kei Ito, Hideki Kise, Satoshi Suzuki, Sota Nagai, Kurenai Hachiya, Hiroki Takeda, Soya Kawabata, Daiki Ikeda, Keiyo Takubo, Shinjiro Kaneko, Nobuyuki Fujita
Summary: Oxidative stress plays a role in degenerative musculoskeletal conditions, including lumbar spinal canal stenosis. This study aimed to investigate the connection between oxidative stress and hypertrophy of the ligamentum flavum (LF) in the lumbar spine. The findings suggest that oxidative stress may be a therapeutic target for LF hypertrophy, and the antioxidant N-acetylcysteine shows potential as a treatment for lumbar spinal canal stenosis.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Biology
Sho Sugawara, Ryo Okada, Tze Mun Loo, Hisamichi Tanaka, Kenichi Miyata, Masatomo Chiba, Hiroko Kawasaki, Kaoru Katoh, Shizuo Kaji, Yoshiro Maezawa, Koutaro Yokote, Mizuho Nakayama, Masanobu Oshima, Koji Nagao, Chikashi Obuse, Satoshi Nagayama, Keiyo Takubo, Akira Nakanishi, Masato T. Kanemaki, Eiji Hara, Akiko Takahashi
Summary: The downregulation of RNaseH2A promotes the development of the senescence-associated secretory phenotype (SASP) by accumulating nucleotide ligands (rNMPs), contributing to the pathological features of senescent, progeroid, and cancer cells.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Noriko Miyake, Yoshinori Tsurusaki, Ryoko Fukai, Itaru Kushima, Nobuhiko Okamoto, Kei Ohashi, Kazuhiko Nakamura, Ryota Hashimoto, Yoko Hiraki, Shuraku Son, Mitsuhiro Kato, Yasunari Sakai, Hitoshi Osaka, Kimiko Deguchi, Toyojiro Matsuishi, Saoko Takeshita, Aviva Fattal-Valevski, Nina Ekhilevitch, Jun Tohyama, Patrick Yap, Wee Teik Keng, Hiroshi Kobayashi, Keiyo Takubo, Takashi Okada, Shinji Saitoh, Yuka Yasuda, Toshiya Murai, Kazuyuki Nakamura, Shouichi Ohga, Ayumi Matsumoto, Ken Inoue, Tomoko Saikusa, Tova Hershkovitz, Yu Kobayashi, Mako Morikawa, Aiko Ito, Toshiro Hara, Yota Uno, Chizuru Seiwa, Kanako Ishizuka, Emi Shirahata, Atsushi Fujita, Eriko Koshimizu, Satoko Miyatake, Atsushi Takata, Takeshi Mizuguchi, Norio Ozaki, Naomichi Matsumoto
Summary: Autism spectrum disorder (ASD) is caused by a combination of genetic and environmental factors. By analyzing 405 ASD patients, researchers identified disease-causing single-nucleotide variants (SNVs), small insertions and deletions (indels), and copy number variations (CNVs) for molecular diagnoses. They achieved a molecular diagnosis in 16.3% of the patients and found a higher diagnostic rate in females and in simplex cases compared to multiplex families.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Hematology
Kohei Shiroshita, Hiroshi Kobayashi, Shintaro Watanuki, Daiki Karigane, Yuriko Sorimachi, Shinpei Tamaki, Miho Haraguchi, Masamichi Yamamoto, Ayako Nakamura-Ishizu, Shinichiro Okamoto, Keisuke Kataoka, Keiyo Takubo
Summary: In physiological conditions, most adult hematopoietic stem cells (HSCs) maintain a quiescent state. The role of the preparatory phase of glycolysis in maintaining HSCs is unknown. However, in this study, it was found that the payoff phase is vital for HSC function, while the preparatory phase is essential for HSC survival. These findings reveal new insights into HSC metabolism regulation and could contribute to the development of novel therapies for hematologic disorders.
EXPERIMENTAL HEMATOLOGY
(2023)
Article
Cell & Tissue Engineering
Yuriko Sorimachi, Hiroshi Kobayashi, Yusuke Shiozawa, Shuhei Koide, Ryuichiro Nakato, Yukiko Shimizu, Tadashi Okamura, Katsuhiko Shirahige, Atsushi Iwama, Nobuhito Goda, Kaiyo Takubo, Keiyo Takubo
Summary: This study found that the loss of p53 in mesenchymal stem cells (MSCs) mainly causes adult undifferentiated soft tissue sarcoma (USTS). MSCs lacking p53 show changes in stem cell properties, including differentiation, cell cycle progression, and metabolism. The transcriptomic changes and genetic mutations in murine p53-deficient USTS mimic those seen in human STS. Single-cell RNA sequencing revealed that MSCs undergo transcriptomic alterations with aging, a risk factor for certain types of USTS, and that p53 signaling decreases simultaneously. Moreover, human STS can be transcriptomically classified into six clusters with different prognoses, different from the current histopathological classification. This study paves the way for understanding MSC-mediated tumorigenesis and provides an efficient mouse model for sarcoma studies.
Article
Biochemical Research Methods
Kohei Shiroshita, Hiroshi Kobayashi, Keiyo Takubo
Summary: This article presents a protocol for optimizing genome editing conditions for murine hematopoietic stem cells (HSCs) based on non-homologous end joining (NHEJ), and evaluates the functionality of edited HSCs. The protocol includes steps for sgRNA preparation, cell sorting, preculture, and electroporation, as well as details on post-editing culture and bone marrow transplantation. It can be used to study genes related to HSC quiescence.
Article
Multidisciplinary Sciences
Keiyo Takubo, Phyo Wai Htun, Takeshi Ueda, Yasuyuki Sera, Masayuki Iwasaki, Miho Koizumi, Kohei Shiroshita, Hiroshi Kobayashi, Miho Haraguchi, Shintaro Watanuki, Zen-ichiro Honda, Norimasa Yamasaki, Ayako Nakamura- Ishizu, Fumio Arai, Noboru Motoyama, Tomohisa Hatta, Tohru Natsume, Toshio Suda, Hiroaki Honda
Summary: The gene Mbtd1 plays a crucial role in regulating the number and function of hematopoietic stem cells. In mice deficient in Mbtd1, the numbers of stem cells and progenitors increase, and these deficient stem cells exhibit an overactive cell cycle and impaired response to stress. The study also shows that Mbtd1 is directly involved in maintaining cell cycle quiescence by binding to the promoter region of the FoxO3a gene, which is essential for the normal function of hematopoietic stem cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemical Research Methods
Kohei Shiroshita, Hiroshi Kobayashi, Shintaro Watanuki, Daiki Karigane, Yuriko Sorimachi, Shinya Fujita, Shinpei Tamaki, Miho Haraguchi, Naoki Itokawa, Kazumasa Aoyoama, Shuhei Koide, Yosuke Masamoto, Kenta Kobayashi, Ayako Nakamura-Ishizu, Mineo Kurokawa, Atsushi Iwama, Shinichiro Okamoto, Keisuke Kataoka, Keiyo Takubo
Summary: This study presents a platform for analyzing the quiescence of hematopoietic stem cells (HSCs) by combining culture conditions and a CRISPR-Cas9 genome editing system. The study demonstrates that preculturing HSCs enhances editing efficiency and that low-cytokine culture conditions better preserve the phenotypes and quiescence of edited HSCs.
CELL REPORTS METHODS
(2022)
Meeting Abstract
Hematology
Kohei Shiroshita, Hiroshi Kobayashi, Daiki Karigane, Keiyo Takubo
EXPERIMENTAL HEMATOLOGY
(2022)
