Article
Biochemistry & Molecular Biology
Chaonan Liu, Weinian Liao, Jun Chen, Shuzhen Zhang, Mo Chen, Fang Chen, Tianmin Cheng, Junping Wang, Changhong Du
Summary: There is a growing understanding of the role of hematopoietic alterations in the detrimental effects of metabolic disorders. This study reveals that hematopoietic stem cells in the bone marrow have distinct cholesterol metabolic signatures and that cholesterol directly regulates their maintenance and lineage differentiation. The study also uncovers the mechanisms by which cholesterol enhances ferroptosis resistance and promotes myeloid lineage differentiation while dampening lymphoid lineage differentiation. These findings have important clinical implications for understanding and treating metabolic disorders.
Review
Hematology
Laura R. Goldberg
Summary: Extracellular vesicles (EVs) play a critical role in modulating hematopoiesis within the bone marrow microenvironment and may be key mediators of HSC aging. Studies have shown their involvement in numerous age-related biologic processes and diseases, influencing both normal and malignant hematopoiesis.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Lakshmi Reddy Palam, Baskar Ramdas, Katelyn Pickerell, Santhosh Kumar Pasupuleti, Rahul Kanumuri, Annamaria Cesarano, Megan Szymanski, Bryce Selman, Utpal P. Dave, George Sandusky, Fabiana Perna, Sophie Paczesny, Reuben Kapur
Summary: Loss of function mutations in DNMT3A are commonly found in AML patients with normal cytogenetics and are associated with poor prognosis. In this study, we found that loss of Dnmt3a resulted in myeloproliferation and hyperactivation of the PI3K pathway. Treatment with PI3K inhibitors partially corrected myeloproliferation, with the alpha/beta inhibitor being more effective. Additionally, PI3K inhibitor treatment prolonged survival and reduced leukemic burden in a human DNMT3A mutant AML model.
Article
Cell & Tissue Engineering
Jing Zhang, Yaozhen Chen, Dandan Yin, Fan Feng, Qunxing An, Zhixin Liu, Ning An, Jinmei Xu, Jing Yi, Shunli Gu, Wen Yin, Yazhou Wang, Xingbin Hu
Summary: The fate of hematopoietic stem cells is influenced by a complex network of intrinsic and extrinsic signals, with mesenchymal stromal cells playing a crucial role in regulating hematopoiesis. Knockout of Caspase-3 and NLRP3 genes in mice has revealed their importance in myeloid lineage expansion and hematopoietic progenitor development. These findings provide new insights into the regulatory mechanisms of physiological hematopoiesis in the bone marrow.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Oncology
Eline J. M. Bertrums, Axel K. M. Rosendahl Huber, Jurrian K. de Kanter, Arianne M. Brandsma, Anais J. C. N. van Leeuwen, Mark Verheul, Marry M. van den Heuvel-Eibrink, Rurika Oka, Markus J. van Roosmalen, Hester A. de Groot-Kruseman, C. Michel Zwaan, Bianca F. Goemans, Ruben van Boxtel
Summary: This study reveals that chemotherapy increases the mutation burden of normal blood cells in cancer survivors, and most of these additional mutations are induced by processes similar to those present during normal aging.
Article
Cell Biology
Oscar A. Pena, Alexandra Lubin, Jasmine Rowell, Yvette Hoade, Noreen Khokhar, Hanna Lemmik, Christopher Mahony, Phoebe Dace, Chianna Umamahesan, Elspeth M. Payne
Summary: Germline loss or mutation of one copy of the transcription factor GATA2 in humans results in clinical phenotypes affecting hematopoietic, lymphatic, and vascular systems. In this research, zebrafish with two copies of the Gata2 gene were used to investigate the effects of these genes on hematopoiesis during development, revealing unique roles at different stages and a potential redundancy between the two genes. The study also showed defects in the myeloid compartment in adult zebrafish with combined heterozygosity loss, similar to GATA2 loss in humans, adding to our understanding of GATA2 deficiency and its developmental effects.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Ram Lakhan, Chozha V. Rathinam
Summary: Deletion of canonical notch pathways in hematopoietic stem cells leads to compromised HSC maintenance and functions in response to stressors, while upregulating key notch target genes and increasing notch activity, which establish a functional link between Hif and Notch pathways in hematopoiesis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Takeshi Fujino, Shuhei Asada, Susumu Goyama, Toshio Kitamura
Summary: This review discusses the causes of hematopoietic stem cell aging, including both intrinsic and extrinsic factors. Epigenetics and inflammation have been found to be involved in the connection between HSC aging, clonality, and oncogenesis. Clarifying the mechanisms of HSC aging has accelerated the development of therapeutic interventions for rejuvenating HSCs.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
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)
Review
Biochemistry & Molecular Biology
Claudia Morganti, Keisuke Ito
Summary: Mitochondrial dysfunction and stem cell exhaustion are characteristic features of aging, particularly in the hematopoietic system. Understanding the key mechanisms of HSC aging, including mitochondrial ROS production and alterations in metabolism, could lead to the identification of new therapeutic targets to prevent, delay, or reverse aspects of the aging process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Engineering, Environmental
Yuanyuan Wang, Xiaoting Jin, Min Li, Jie Gao, Xingchen Zhao, Juan Ma, Chunzhen Shi, Bin He, Ligang Hu, Jianbo Shi, Guoliang Liu, Guangbo Qu, Yuxin Zheng, Guibin Jiang
Summary: Pulmonary exposure to PM2.5 induces stress hematopoiesis dependent on NRF2 in the lungs and bone marrow, resulting in related health outcomes. The detailed alterations in systemic hematopoiesis and the underlying mechanisms under PM2.5 exposure are still unclear. NRF2 is essential for regulating hematopoiesis under steady-state or stress conditions, but upon PM2.5 exposure, it is involved in stress myelopoiesis and enhanced PM2.5 toxicity, leading to systemic inflammation.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2023)
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.
Article
Oncology
Stefania Trino, Ilaria Laurenzana, Daniela Lamorte, Giovanni Calice, Angelo De Stradis, Michele Santodirocco, Alessandro Sgambato, Antonella Caivano, Luciana De Luca
Summary: This study reveals that AML cells disrupt the hematopoietic process of HSPCs by releasing EVs, which alter gene expression and affect the phenotype and function of HSPCs. This communication may contribute to the formation of a leukemic niche favorable for leukemia development.
FRONTIERS IN ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Shokrollah Elahi
Summary: Under physiological conditions, HSPCs in the bone marrow niches are responsible for regulating hematopoiesis, but they can be influenced by microbial agents and infection-induced mediators. This article reviews the impact of these factors on hematopoiesis and discusses how SARS-CoV-2 infection alters the hematopoietic system, including lymphopenia, thrombocytopenia, and hypercoagulability.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Pascal Fichtel, Malte von Bonin, Robert Kuhnert, Kristin Moebus, Martin Bornhaeuser, Manja Wobus
Summary: Aging of the hematopoietic system is characterized by an expansion of hematopoietic stem and progenitor cells (HSPCs) with reduced capacity for engraftment, self-renewal, and lymphoid differentiation, resulting in myeloid-biased hematopoiesis.
The communication between HSPCs and MSCs is mediated by direct cell-cell contacts or extracellular vesicles (EVs) that carry bioactive substances. Aging MSCs secrete fewer miRNAs, but aged MSC-EVs contain higher levels of specific miRNAs such as miR-29a and miR-34a. Young EVs enhance the cell number and viability of HSPCs, while aged MSC-EVs promote the differentiation of HSPCs into erythroid and erythroid-megakaryocytic progenitor cells. The therapeutic relevance of MSC-derived EVs in modulating HSPC characteristics needs further investigation.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
