Article
Multidisciplinary Sciences
Martin L. Rennie, Connor Arkinson, Viduth K. Chaugule, Helen Walden
Summary: In this study, the enzyme-substrate-inhibitor complex of USP1 and the well-established inhibitor, ML323, was studied using cryo-electron microscopy. A novel binding mode of the inhibitor disrupting part of the hydrophobic core of USP1 was revealed, leading to subtle rearrangements in the active site and elucidating the mechanism of inhibition.
Article
Biochemistry & Molecular Biology
Martin L. Rennie, Connor Arkinson, Viduth K. Chaugule, Rachel Toth, Helen Walden
Summary: Structures of USP1-UAF complexes, including a cryo-EM structure of USP-UAF1 bound to its substrate FANCI-FANCD2, provide molecular details of USP1-UAF1 regulation and substrate recognition, shedding light on its role in DNA repair processes.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Genetics & Heredity
Takahiro Sano, Koki Ueda, Keiji Minakawa, Tsutomu Mori, Yuko Hashimoto, Haruhiko Koseki, Yasuchika Takeishi, Kazuhiko Ikeda, Takayuki Ikezoe
Summary: This study generated Uhrf2(-/-) mice to investigate the role of UHRF2 deletion in hematopoiesis. The results showed that the absence of UHRF2 did not affect blood counts, bone marrow findings, and spleen weights. However, the proportions of Uhrf2(-/-) cells were decreased compared to Uhrf2(+/+) cells in competitive repopulation assays, indicating a potential regulatory role of UHRF2 in hematopoiesis.
Article
Biochemistry & Molecular Biology
Seok Won Jang, Jung Min Kim
Summary: The study found that Asp-199 plays a crucial role in the activity of USP1. The D199A mutation renders USP1 inactive, does not affect the interaction with Uaf1, but impacts the deubiquitination activity of FANCD2 and PCNA.
Article
Cell Biology
Na Yuan, Wen Wei, Li Ji, Jiawei Qian, Zhicong Jin, Hong Liu, Li Xu, Lei Li, Chen Zhao, Xueqin Gao, Yulong He, Mingyuan Wang, Longhai Tang, Yixuan Fang, Jianrong Wang
Summary: The bone marrow niche, responsible for maintaining hematopoietic stem cell homeostasis, declines in function with aging and hematological malignancies. This study reveals that disrupting autophagy in HSCs accelerates niche aging, while transplantation of young donor HSCs repairs the niche environment. Further investigation shows that HSCs transdifferentiate into functional niche cells, including mesenchymal stromal cells and endothelial cells, in an autophagy-dependent manner. These findings provide a clinical solution to rejuvenate an aged or damaged bone marrow hematopoietic niche.
Review
Biochemistry & Molecular Biology
Masayuki Yamashita, Atsushi Iwama
Summary: This review summarizes the changes in hematopoietic stem cells (HSCs) during aging and how different clones of HSCs can be expanded. Research shows that in mice and humans, the clonal behavior of HSCs is closely related to the risk of hematological malignancies and cardiovascular diseases. Therefore, understanding the impact of aging on the hematopoietic system is critical to prevent or overcome age-related changes in the blood.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Alessandro Marins-Dos-Santos, Jackline de Paula Ayres-Silva, Dina Antunes, Carlos Jose de Carvalho Moreira, Marcelo Pelajo-Machado, David Alfaro, Agustin G. Zapata, Adriana Cesar Bonomo, Wilson Savino, Juliana de Meis, Desio Aurelio Farias-de-Oliveira
Summary: This study demonstrates that Trypanosoma cruzi causes high tissue parasitism during the acute phase of Chagas disease. In mice with acute oral infection, the bone marrow cells are highly parasitized, particularly in the perivascular, intravascular, and near bone regions. The infection leads to a decrease in hematopoietic cells in the bone marrow, except for an increase in hematopoietic stem and progenitor cells. The study also suggests that the spleen may play a role in emergency hematopoiesis during acute T. cruzi infection. Overall, this research provides important insights into the impact of T. cruzi infection on the hematopoietic system.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Govinda Bhattarai, Han-Sol So, Tae-Geum Kim, Thi Thu Trang Kieu, Yeon-Woo Kim, Ku-Ri Yang, Jeong-Chae Lee, Sung-Ho Kook, Young-Mi Jeon
Summary: Astaxanthin (ASTX) can alleviate hyperglycemia-induced damage to bone marrow and stem cells, restoring normal hematopoiesis and bone accrual.
Article
Oncology
Makiko Mochizuki-Kashio, Noriko Otsuki, Kota Fujiki, Sherif Abdelhamd, Peter Kurre, Markus Grompe, Atsushi Iwama, Kayoko Saito, Ayako Nakamura-Ishizu
Summary: Fanconi Anemia (FA) is a genetic bone marrow failure disorder commonly diagnosed in school age children. Mitochondrial metabolism and mitophagy play important roles in long-term hematopoietic stem cell (HSC) function. Impaired mitophagy has been observed in FA cells. This study found that replication stress (RS) activates mitochondrial metabolism and mitophagy in HSC, and that FL HSCs deficient in FANCD2 show increased mitochondrial metabolism and mitophagy while adult FANCD2-deficient BM HSCs exhibit decreased mitophagy.
FRONTIERS IN ONCOLOGY
(2023)
Article
Cell & Tissue Engineering
Wei Shan, Qin Yu, Yan Long, Qian Luo, Honghu Li, Yingli Han, Yulin Xu, Shan Fu, Xiangjun Zeng, Cong Wei, Yang Gao, Xiaoqing Li, Xia Li, Lifei Zhang, Lizhen Liu, Ming Chen, Pengxu Qian, He Huang
Summary: This study established an in vitro differentiation system that successfully generated hematopoietic cells with in vivo hematopoietic reconstitution potential from mouse PSCs. The combination of 3D induction system and OP9 stromal cell coculture yielded c-kit(+) cells with superior repopulating activity.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Imtiaz Iftakhar-e-Khuda, Alberto Pessia, Shuyu Zheng, Matti Kankainen, Mika Kontro, Marika Karikoski, Juha Laurila, Heidi Gerke, Sina Tadayon, Maija Hollmen, Jing Tang, Beat A. Imhof, Marko Salmi, Sirpa Jalkanen
Summary: This study demonstrates that Vascular Adhesion Protein-1 (VAP-1) is expressed on a subset of human hematopoietic stem cells (HSC) and bone marrow vasculature, playing a role in regulating HSC proliferation through the p53 signaling pathway. Inhibition of VAP-1 enhances HSC expansion and differentiation, suggesting its potential as a target for HSC manipulation and therapy.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Multidisciplinary Sciences
Meenal Francis, Smitha Bhaskar, Saarwani Komanduri, Preethi Sheshadri, Jyothi Prasanna, Anujith Kumar
Summary: Loss of insulin-secreting beta-cells in diabetes can be caused by apoptosis or dedifferentiation. This study identifies USP1 as a key regulator of beta-cell dedifferentiation, and inhibition of USP1 can restore the epithelial phenotype of beta-cells. Furthermore, USP1 mediates its effect through modulation of the expression of inhibitor of differentiation 2 (ID2). Administering the USP1 inhibitor ML323 in a dedifferentiation mouse model alleviated hyperglycemia, suggesting its potential therapeutic application in reducing beta-cell loss during diabetes.
Article
Biochemistry & Molecular Biology
Diego A. Lopez, Kelly S. Otsuka, April C. Apostol, Jasmine Posada, Juan C. Sanchez-Arcila, Kirk D. C. Jensen, Anna E. Beaudin
Summary: This study investigates the fetal hematopoietic response to maternal infection with Toxoplasma gondii. The results show that fetal HSCs respond to infection with changes in proliferation, self-renewal potential, and lineage output. Maternal IFN gamma crosses the fetal-maternal interface and is perceived by fetal HSCs.
Article
Immunology
Xiaotong Zhu, Peng Wang, Xiaoxia Zhan, Yuping Zhang, Junli Sheng, Shitong He, Yitian Chen, Dingnai Nie, Xiaolong You, Haiyan Mai, Qinghong Yu, Laisheng Li, Ligang Jie, Shengfeng Hu
Summary: This study identified ubiquitin-specific peptidase 1 (USP1) as a critical regulator of CD4(+) T-cell differentiation, promoting Th17-cell differentiation and attenuating Treg-cell differentiation, thereby promoting the development of inflammatory diseases. The specific inhibitor ML323 was found to inhibit Th17-cell differentiation and promote Treg-cell differentiation, suggesting its potential as a candidate for the treatment of diseases associated with an imbalance between Th17 and Treg cells.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Article
Medicine, General & Internal
Yufeng Hu, Xiaodong Cheng
Summary: This study investigated the expression of UBE2T, FANCD2, and USP1 in cervical squamous cell carcinoma and precancerous lesions, and found that their expression levels were associated with clinicopathological factors, suggesting potential clinical significance.
ACTA MEDICA MEDITERRANEA
(2021)
