Article
Cell Biology
Daniel C. L. Robinson, Morten Ritso, Geoffrey M. Nelson, Zeinab Mokhtari, Kiran Nakka, Hina Bandukwala, Seth R. Goldman, Peter J. Park, Remi Mounier, Benedicte Chazaud, Marjorie Brand, Michael A. Rudnicki, Karen Adelman, F. Jeffrey Dilworth
Summary: In this study, muscle-stem-cell-specific deletion of NELF showed its critical role in efficient muscle regeneration and stem cell pool replenishment. Mechanistic studies revealed that NELF modulates p53 signaling to promote the expansion of muscle progenitors during regeneration. Transplantation experiments indicated that progenitors returning to quiescence are major contributors to stem cell pool repopulation.
DEVELOPMENTAL CELL
(2021)
Article
Multidisciplinary Sciences
Amit K. Singh, Qingrong Chen, Cu Nguyen, Daoud Meerzaman, Dinah S. Singer
Summary: Cohesin plays a role in regulating alternative splicing by interacting with splicing factors and influencing splicing patterns. Mutations in cohesin are associated with distinct splicing patterns in acute myeloid leukemia, and cohesin interacts with another splicing regulator, BRD4, to generate unique splicing patterns. These findings provide insights into the role of cohesin in both normal and leukemic cells and its contribution to human disease.
Article
Cell Biology
Rebekah Eleazer, Kalpani De Silva, Kalina Andreeva, Zoe Jenkins, Nour Osmani, Eric C. Rouchka, Yvonne Fondufe-Mittendorf
Summary: Circular RNAs (circRNAs), derived from protein-coding genes, play important roles in biology and pathology. The mechanism behind their formation through backsplicing is still unclear. Factors that regulate pre-mRNA transcription and splicing, including RNAPII kinetics, splicing factors, and gene architecture, influence backsplicing decisions. This study investigated the role of PARP1 in circRNA biogenesis and found that PARP1 regulates circRNA production through its influence on RNAPII pausing and gene architecture. This regulation fine-tunes transcriptional output and affects gene function.
Article
Oncology
Yukai Lu, Lijing Yang, Mingqiang Shen, Zihao Zhang, Song Wang, Fang Chen, Naicheng Chen, Yang Xu, Hao Zeng, Mo Chen, Shilei Chen, Fengchao Wang, Mengjia Hu, Junping Wang
Summary: This study reveals that Tespa1 is important for the maintenance of hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs) and plays a crucial role in HSC and LSC self-renewal. Tespa1 prevents degradation of c-Myc protein in HSCs and is essential for AML cell growth. Tespa1 deficiency suppresses leukemogenesis and LSC maintenance.
Article
Hematology
Christina M. Termini, Amara Pang, Michelle Li, Tiancheng Fang, Vivian Y. Chang, John P. Chute
Summary: The discovery of Syndecan-2 as a novel surface marker and regulator of hematopoietic stem cell (HSC) function has improved the understanding of HSC identity and their capacity for repopulation. Syndecan-2 expression is significantly increased in long-term HSCs compared to differentiated hematopoietic cells. Isolation of bone marrow cells based on Syndecan-2 expression results in a higher enrichment of HSCs with superior in vivo repopulating capacity, compared to conventional selection methods. Syndecan-2 regulates HSC repopulating capacity through control of Cdkn1c expression and HSC quiescence.
Article
Oncology
Zihao Zhang, Yukai Lu, Yan Qi, Yang Xu, Song Wang, Fang Chen, Mingqiang Shen, Mo Chen, Naicheng Chen, Lijing Yang, Shilei Chen, Fengchao Wang, Yongping Su, Mengjia Hu, Junping Wang
Summary: CDK19 is involved in the regulation of HSC and AML cell proliferation via the p53-p21 pathway.
Article
Biochemistry & Molecular Biology
Kirsten A. Reimer, Claudia A. Mimoso, Karen Adelman, Karla M. Neugebauer
Summary: The study revealed tight coordination between co-transcriptional splicing and transcription elongation and 3' end formation in mammalian cells, with splicing delays possibly taking place between the two catalytic steps. Additionally, inefficient 3' end cleavage was associated with intron retention, highlighting the functional coupling between these co-transcriptional processes.
Article
Multidisciplinary Sciences
Christina M. Termini, Amara Pang, Tiancheng Fang, Martina Roos, Vivian Y. Chang, Yurun Zhang, Nicollette J. Setiawan, Lia Signaevskaia, Michelle Li, Mindy M. Kim, Orel Tabibi, Paulina K. Lin, Joshua P. Sasine, Avradip Chatterjee, Ramachandran Murali, Heather A. Himburg, John P. Chute
Summary: Ionizing radiation and chemotherapy deplete hematopoietic stem cells and damage the vascular niche, leading to the secretion of SEMA3A from bone marrow endothelial cells. Inhibition of NRP1 promotes vascular and hematopoietic regeneration through increased expression of R spondin 2, suggesting a potential therapeutic target for improving hematopoietic recovery after myeloablation.
NATURE COMMUNICATIONS
(2021)
Article
Physics, Fluids & Plasmas
Jin Qian, David Dunlap, Laura Finzi
Summary: In this study, a thermodynamic model of transcriptional pausing is proposed to describe the kinetics of different types of pauses based on the thermal energy of transcription bubbles and nascent RNA structures. The model can accurately predict experimentally detected pauses and the effects of tension and transcription factors on pausing.
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
Biology
A. Lorzadeh, C. Hammond, F. Wang, D. J. H. F. Knapp, J. Ch Wong, J. Y. A. Zhu, Q. Cao, A. Heravi-Moussavi, A. Carles, M. Wong, Z. Sharafian, J. Steif, M. Moksa, M. Bilenky, P. M. Lavoie, C. J. Eaves, M. Hirst
Summary: By generating comprehensive reference epigenomes of normal human cord blood, we have identified differences in chromatin modifications between different cell types. Particularly, the repressive H3K27me3 mark is retained in lymphoid cells but lost in monocytes and erythroblasts. Inhibition of polycomb group members also affects the fate decisions of neonatal hematopoietic progenitor cells.
Article
Multidisciplinary Sciences
Ting Zhang, Carsten Kuenne, Dong Ding, Stefan Guenther, Xinyue Guo, Yonggang Zhou, Xuejun Yuan, Thomas Braun
Summary: This study reveals the crucial role of KMT5B in maintaining genome stability by repressing S-phase transcription through the control of H4K20me1 levels. Loss of KMT5B leads to genome instability and the formation of rhabdomyosarcoma in muscle stem cells.
NATURE COMMUNICATIONS
(2022)
Review
Cell Biology
Bai Ling, Yunyang Xu, Siyuan Qian, Ze Xiang, Shihai Xuan, Jian Wu
Summary: Hematopoietic stem cells (HSCs) play a crucial role in the hematopoietic system as they can self-renew and differentiate into various blood cells. The mTOR signaling pathway is an important regulator of HSCs' differentiation, self-renewal, and quiescence, and several molecules can modulate these potentials by influencing this pathway. This review discusses the regulation of HSCs' three potentials by the mTOR signaling pathway and highlights potential regulators. Additionally, the clinical significance of studying this regulation and future predictions are also outlined.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biology
Shichao Yu, Fangzhou Luo, Li Hua Jin
Summary: This study investigated the role of endosome markers Rab5 and Rab11 in hematopoiesis in Drosophila, revealing their regulatory effects on cell proliferation, lamellocyte formation, and blood cell progenitor maintenance. The findings provide insights into the mechanisms underlying hematopoietic homeostasis and the pathology of blood disorders like leukemia.
Article
Oncology
Ruth Q. Jacobs, Kaila B. Fuller, Stephanie L. Cooper, Zachariah Carter, Marikki Laiho, Aaron L. Lucius, David A. Schneider
Summary: This study evaluates the specificity of the compound BMH-21 on transcription by Pols I, II, and III. The results show that Pol I is more sensitive to inhibition by BMH-21 compared to Pols II and III. These findings support the ongoing development of BMH-21 and its derivatives as potential therapeutic agents.
Article
Hematology
Tongjie Wang, Chengxiang Xia, Qitong Weng, Kaitao Wang, Yong Dong, Sha Hao, Fang Dong, Xiaofei Liu, Lijuan Liu, Yang Geng, Yuxian Guan, Juan Du, Tao Cheng, Hui Cheng, Jinyong Wang
Summary: The study reveals a new role for the Nupr1 gene in regulating the quiescence of hematopoietic stem cells (HSC), which can have implications for improving HSC transplantation efficacy. The deletion of the Nupr1 gene activates dormant HSC and provides a competitive advantage in transplantation without compromising their stemness or differentiation capacity. In addition, the inhibition of Nupr1 affects HSC proliferation and engraftment. This finding could contribute to enhancing the success of HSC transplantation.
Article
Cell Biology
Pengfei Qin, Yakun Pang, Wenhong Hou, Ruiqing Fu, Yingchi Zhang, Xuefei Wang, Guofeng Meng, Qifa Liu, Xiaofan Zhu, Ni Hong, Tao Cheng, Wenfei Jin
Summary: Single-cell RNA sequencing technology was used to analyze the relationship between hematopoiesis and leukemogenesis, revealing different healthy counterparts for leukemia cell subpopulations in different patients and providing insights into the origin of leukemia heterogeneity. The study also developed a framework to predict leukemia subtypes, cellular heterogeneity, and cellular stemness, offering new directions for leukemia research and treatment.
Article
Biotechnology & Applied Microbiology
Mei Zhao, Yi-Dan Sun, Mengdi Yin, Juan-Juan Zhao, Si-Ang Li, Guohua Li, Feng Zhang, Jing Xu, Fei-Ying Meng, Beldon Zhang, Xin-Yu Sun, Jian-Ping Zhang, Tao Cheng, Xiao-Bing Zhang
Summary: This study successfully treated hemophilia A in a mouse model using a gene-editing strategy and identified the humoral immune response as the main cause of decreased treatment efficacy. The findings highlight the importance of modulating the innate immune response triggered by liver damage.
HUMAN GENE THERAPY
(2022)
Article
Oncology
Shengnan Yuan, Xiaomin Wang, Shuaibing Hou, Tengxiao Guo, Yanjie Lan, Shuang Yang, Fei Zhao, Juan Gao, Yuxia Wang, Yajing Chu, Jun Shi, Tao Cheng, Weiping Yuan
Summary: The study indicates that patients with co-mutations of JAK3 and PHF6 have shorter survival times, suggesting a potential role of PHF6 in leukemia progression. Phf6 deficiency promotes JAK3(M511I)-induced T-ALL progression by inhibiting the Bai1-Mdm2-P53 signaling pathway independent of the JAK3/STAT5 signaling pathway. Combination therapy with JAK3 and MDM2 inhibitors may potentially increase the drug benefit for T-ALL patients with PHF6 and JAK3 co-mutations.
Article
Oncology
Yasushige Aoyagi, Yoshihiro Hayashi, Yuka Harada, Kwangmin Choi, Natsumi Matsunuma, Daichi Sadato, Yuki Maemoto, Akihiro Ito, Shigeru Yanagi, Daniel T. Starczynowski, Hironori Harada
Summary: We demonstrated that excessive mitochondrial fragmentation is a fundamental pathobiological phenomenon that could trigger dysplasia formation and ineffective hematopoiesis in MDS. Our findings provide mechanistic insights into ineffective hematopoiesis and suggest dysregulated mitochondrial dynamics as a therapeutic target for treating MDS.
Article
Oncology
Fang Hong, Qianqian Meng, Weiyu Zhang, Ruiqin Zheng, Xiaoyun Li, Tao Cheng, Deqing Hu, Xin Gao
Summary: Single-cell sequencing has provided new insights into the investigation of tumor immune microenvironments (TIME). This study established a pan-cancer single-cell reference of TIMEs, identified new cell type-specific transcription factors, and compared the variation of immune cell types across different patients and tumor types. The study also highlighted the role of tumor-associated macrophages in regulating dysfunctional T cells and the tumor-type specific ligand-receptor communication network within TIMEs.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Oncology
Kazuharu Kamachi, Hiroshi Ureshino, Tatsuro Watanabe, Nao Yoshida, Yuta Yamamoto, Yuki Kurahashi, Yuki Fukuda-Kurahashi, Yoshihiro Hayashi, Hideyo Hirai, Satoshi Yamashita, Toshikazu Ushijima, Seiji Okada, Shinya Kimura
Summary: Targeting DNMT1 with OR21 demonstrates anti-tumor effects and impairs leukemic stem cells in chronic myeloid leukemia (CML). Combination therapy of OR21 and TKIs represents a promising treatment strategy for CML.
Review
Oncology
Yoshihiro Hayashi, Yuka Harada, Hironori Harada
Summary: RUNX1 is a critical transcription factor in hematopoiesis with both regulatory and leukemogenic roles. Genetic alterations in RUNX1 have been identified in various diseases, and recent studies have revealed a wide range of mutations associated with RUNX1. This review highlights the importance of RUNX1 in hematopoiesis and its role in disease development.
Article
Medicine, Research & Experimental
Wenwen Wei, Shujuan Huang, Qing Ling, Shihui Mao, Yu Qian, Wenle Ye, Fenglin Li, Jiajia Pan, Xiangjie Lin, Jiansong Huang, Xin Huang, Yifan Zhai, Jie Sun, Jie Jin
Summary: The combination of APG-2575 and HHT showed synergistic inhibition of AML cell growth and engraftment, providing a potential AML treatment strategy.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Hematology
Yi Zhang, Hu Zhou, Zhongxing Jiang, Dengshu Wu, Junling Zhuang, Wei Li, Qian Jiang, Xiuli Wang, Jinwen Huang, Huanling Zhu, Linhua Yang, Xin Du, Fei Li, Ruixiang Xia, Feng Zhang, Jianda Hu, Yan Li, Yu Hu, Jing Liu, Chenghao Jin, Kai Sun, Zeping Zhou, Liqing Wu, Wenjuan Yu, Jie Jin
Summary: The study demonstrates that Jaktinib is an effective treatment for myelofibrosis, reducing spleen volume, improving anemia, and alleviating symptoms with good tolerability.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Letter
Hematology
Huafeng Wang, Yiyi Yao, Liping Mao, Yinjun Lou, Yanling Ren, Xingnong Ye, Min Yang, Liya Ma, Yi Zhang, Yile Zhou, Jiaying Wu, Xin Huang, Yungui Wang, Huan Xu, Hongyan Tong, Hong-Hu Zhu, Jie Jin
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Hematology
Xiang Zhang, Ziwei Wang, Jiewen Sun, Lixia Liu, Jiayue Qin, Aijie Huang, Min Yang, Yinjun Lou, Gusheng Tang, Liping Mao, Jiejin Qian, Juying Wei, Wenyuan Mai, Haitao Meng, Jianmin Yang, Hongyan Tong, Jianmin Wang, Wenjuan Yu, Xiong Ni, Jie Jin
Summary: As reported, SETD2 is frequently mutated in acute myeloid leukemia (AML), but there is limited knowledge about the specifics. In our study of 530 newly diagnosed AML patients, we found that SETD2 mutation affected 6.3% of patients and often co-occurred with IDH2, NRAS, and CEBPA mutations. Patients with SETD2 mutation had excellent therapeutic responses but did not have better survival time compared to other patients, possibly due to the high recurrence and mortality associated with additional mutations, such as NRAS mutation.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Hematology
Zhixin Ma, Wenle Ye, Jinghan Wang, Xin Huang, Jiansong Huang, Xia Li, Chao Hu, Chenying Li, Yile Zhou, Xiangjie Lin, Wenwen Wei, Yu Qian, Yutong Zhou, Shihui Mao, Xiufeng Yin, Bo Zhu, Jie Jin
Summary: Glutamine metabolic reprogramming in AML cells reduces sensitivity to antileukemic drugs. The enzyme GDH1 plays a role in this process and its high expression is a negative prognostic factor in AML. Inhibition of GDH1 triggers ferroptosis in AML cells, providing a unique therapeutic opportunity.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Review
Oncology
Yoshihiro Hayashi, Hironori Harada
Summary: Myeloid malignancies are a group of hematopoietic stem cell diseases that are associated with global population aging. Mitochondrial involvement in the pathogenesis of myeloid malignancies and aging-related hematopoiesis has been discovered, although the molecular and cellular basis of disease development remains unclear.
Article
Oncology
Wenle Ye, Jinghan Wang, Jiansong Huang, Xiao He, Zhixin Ma, Xia Li, Xin Huang, Fenglin Li, Shujuan Huang, Jiajia Pan, Jingrui Jin, Qing Ling, Yungui Wang, Yongping Yu, Jie Sun, Jie Jin
Summary: Acyl-CoA synthetase long chain family member 5 (ACSL5) is involved in activating long chain fatty acids and has been found to be dysregulated in certain cancers, including glioma and colon cancers. However, its role in acute myeloid leukemia (AML) is not well understood. This study demonstrates that ACSL5 is upregulated in bone marrow cells from AML patients and can serve as an independent prognostic predictor for their overall survival. Inhibition of ACSL5 suppresses AML cell growth through the Wnt/beta-catenin pathway and a combination of ACSL inhibitor and BCL-2 inhibitor shows promise for AML treatment.
FRONTIERS OF MEDICINE
(2023)
