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
Weinian Liao, Chaonan Liu, Ke Yang, Jun Chen, Yiding Wu, Shuzhen Zhang, Kuan Yu, Lisha Wang, Li Ran, Mo Chen, Fang Chen, Yang Xu, Song Wang, Fengchao Wang, Qian Zhang, Jinghong Zhao, Lilin Ye, Changhong Du, Junping Wang
Summary: The accumulation of DNA mutations in aging hematopoietic stem cells (HSCs) increases the expression of MHCII on their surface, allowing them to be recognized by bone marrow regulatory T cells (Tregs). Tregs transfer cAMP to aged HSCs through gap junctions, promoting their survival and preventing apoptosis. Disrupting the interaction between HSCs and Tregs effectively prevents premature/physiological aging of HSCs.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Article
Cell & Tissue Engineering
Yusheng Cai, Si Wang, Jing Qu, Juan Carlos Izpisua Belmonte, Guang-Hui Liu
Summary: Stem cell therapies offer promising approaches for treating various diseases by addressing stem cell exhaustion and dysfunction. Recent advances in understanding the mechanisms of stem cell regeneration and rejuvenation strategies utilizing intrinsic and extrinsic factors may pave the way for interventions to delay aging and treat age-associated diseases.
STEM CELLS TRANSLATIONAL MEDICINE
(2022)
Article
Cell & Tissue Engineering
Novella Guidi, Gina Marka, Vadim Sakk, Yi Zheng, Maria Carolina Florian, Hartmut Geiger
Summary: The study found that an aged niche restrains the function of ex vivo rejuvenated old HSCs, with a low level of the cytokine osteopontin being a contributing factor. Sustainable rejuvenation of the function of aged HSCs in vivo will need to address the influence of an aged niche on rejuvenated HSCs.
Review
Cell Biology
Daozheng Yang, Gerald de Haan
Summary: Hematopoietic stem cells (HSCs) play a crucial role in lifelong blood cell production. Aging impacts HSC function, with inflammation emerging as a key factor in driving this process. Both intrinsic and extrinsic factors contribute to HSC aging.
Review
Biochemistry & Molecular Biology
Daniil Shevyrev, Valeriy Tereshchenko, Tatiana N. Berezina, Stanislav Rybtsov
Summary: Hematopoietic stem cells (HSCs) support hematopoiesis throughout life, but their regenerative potential decreases with age, affecting immune function. The aging of HSCs leads to decreased self-renewal ability, changes in differentiation potential, and a disturbed immune cell formation. This results in increased inflammation and higher risk of age-related diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Geriatrics & Gerontology
Parvaneh Abbasi Sourki, Ali Akbar Pourfathollah, Saeed Kaviani, Mina Soufi Zomorrod, Mansoureh Ajami, Barbara Wollenberg, Gabriele Multhoff, Ali Bashiri Dezfouli
Summary: Blood donor age has a significant impact on the behavior of hematopoietic stem cells (HSCs) due to age-associated variations in plasma-derived extracellular nano-sized vesicles (EVs) content. Young donor EVs improve HSCs' growth and self-renewal potential, while EVs from elderly donors induce senescence-associated differentiation towards the myeloid lineage. This study reveals the role of EVs in delivering youth or aging signals to HSCs and emphasizes the importance of understanding EVs' content for blood transfusion safety and efficacy.
EXPERIMENTAL GERONTOLOGY
(2023)
Article
Genetics & Heredity
Xiangjun Zeng, Xia Li, Mi Shao, Yulin Xu, Wei Shan, Cong Wei, Xiaoqing Li, Limengmeng Wang, Yongxian Hu, Yanmin Zhao, Pengxu Qian, He Huang
Summary: This study identified markers of apoptosis-biased and inflammatory aged HSCs, common differentially expressed genes between young and aged HSCs, and functional enrichment analysis showed involvement in the cell cycle and TNF signaling pathway. The Skp2-induced signaling pathway was found to contribute to rapid transition through G1 phase in aged HSCs, and inflammatory genes in the bone marrow microenvironment were increased in HSC aging. Inflammatory cytokines promoted cellular senescence, but blockade of the inflammatory pathway rejuvenated aged HSC functions and increased B cell output.
FRONTIERS IN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Frauke Gotzhein, Tim Aranyossy, Lars Thielecke, Tanja Sonntag, Vanessa Thaden, Boris Fehse, Ingo Mueller, Ingmar Glauche, Kerstin Cornils
Summary: In this study, a murine model of HSCT was used to investigate the contribution of different hematological subpopulations to the reconstitution process and the impact of age on this process. The results showed that hematopoietic stem cells and multipotent progenitors played a major role in reconstitution, independent of age. The reconstitution patterns were stable in all age groups. These findings support the expansion of HSCT in older individuals as a promising strategy for treating hematological diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Laura Poisa-Beiro, Jonathan J. M. Landry, Simon Raffel, Motomu Tanaka, Judith Zaugg, Anne-Claude Gavin, Anthony D. Ho
Summary: Studies on human hematopoietic stem and progenitor cells (HSPC) have revealed that aging is characterized by increased glycolysis and alterations in gene expression. By analyzing proteomics and single-cell transcriptomics data, researchers have identified the changes in molecular pathways associated with aging. Notably, elevated central carbon metabolism is found to be associated with senescence. The findings provide insights into the aging process and offer a potential method for senescence enrichment in human bone marrow.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Saloni Sinha, Alice Sinha, Prathamesh Dongre, Kajal Kamat, Maneesha S. Inamdar
Summary: Aging of the blood system is characterized by increased hematopoietic stem cells and myeloid-biased differentiation. Asrij/OCIAD1 is a regulator that controls the aging of HSCs by governing organelle function and proteasome activity. Its deletion causes loss of HSC quiescence, myeloid skewing, reduced p53 and increased DNA damage. Asrij regulates p53 ubiquitination and degradation and AKT/STAT5 activation.
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
Cell Biology
Pallavi Budgude, Anuradha Vaidya, Vaijayanti Kale
Summary: Hematopoiesis is a complex process regulated by intrinsic and extrinsic factors. Understanding the dominant intrinsic factors governing the activation and quiescence of hematopoietic stem cells can provide insights for novel therapeutic approaches. This review focuses on recent research on adult HSCs and their associated intrinsic factors.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Oleg Kandarakov, Alexander Belyaysky, Ekaterina Semenova
Summary: This review discusses various aspects of organization and functioning of the HSC cell niche in bone marrow. The studies include the anatomy of BM niches, various cell types composing the niche, niches for more differentiated cells, metabolism of HSCs in relation to the niche, niche aging, and leukemic transformation of the niche.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Mirjam E. Belderbos, Sabrina Jacobs, Taco K. Koster, Albertina Ausema, Ellen Weersing, Erik Zwart, Gerald de Haan, Leonid V. Bystrykh
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
(2020)
Correction
Oncology
Sabrina Jacobs, Albertina Ausema, Erik Zwart, Ellen Weersing, Maaike J. Kingma, Yasmine A. S. El Menshawi, Gerald de Haan, Leonid V. Bystrykh, Mirjam E. Belderbos
Letter
Oncology
Sabrina Jacobs, Albertina Ausema, Erik Zwart, Ellen Weersing, Maaike J. Kingma, Yasmine A. S. El Menshawi, Gerald de Haan, Leonid V. Bystrykh, Mirjam E. Belderbos
Article
Cell Biology
Danielle Gaby Luinenburg, Gerald de Haan
MECHANISMS OF AGEING AND DEVELOPMENT
(2020)
Article
Dentistry, Oral Surgery & Medicine
Paola Serrano Martinez, Davide Cinat, Peter van Luijk, Mirjam Baanstra, Gerald de Haan, Sarah Pringle, Robert P. Coppes
Summary: The study demonstrates the presence of potential stem cells with self-renewal and differentiation capabilities in single cells derived from murine parotid gland organoids. By developing a murine model, it can provide insights into the radiation response of stem cells, offering a useful tool for further mechanistic studies in this area.
Article
Hematology
Sabrina Jacobs, Albertina Ausema, Erik Zwart, Ellen Weersing, Gerald de Haan, Leonid V. Bystrykh, Mirjam E. Belderbos
EXPERIMENTAL HEMATOLOGY
(2020)
Article
Hematology
Danielle G. Luinenburg, Alexander Bak Dinitzen, Arthur Flohr Svendsen, Roza Cengiz, Albertina Ausema, Ellen Weersing, Leonid Bystrykh, Gerald de Haan
Summary: Continuous expression of miR-125a is essential for enhancing HSC activity, with molecular analysis revealing pathway changes and functional alterations caused by overexpression of miR-125a.
EXPERIMENTAL HEMATOLOGY
(2021)
Article
Multidisciplinary Sciences
Simon Renders, Arthur Flohr Svendsen, Jasper Panten, Nicolas Rama, Maria Maryanovich, Pia Sommerkamp, Luisa Ladel, Anna Rita Redavid, Benjamin Gibert, Seka Lazare, Benjamin Ducarouge, Katharina Schoenberger, Andreas Narr, Manon Tourbez, Bertien Dethmers-Ausema, Erik Zwart, Agnes Hotz-Wagenblatt, Dachuan Zhang, Claudia Korn, Petra Zeisberger, Adriana Przybylla, Markus Sohn, Simon Mendez-Ferrer, Mathias Heikenwaelder, Maik Brune, Daniel Klimmeck, Leonid Bystrykh, Paul S. Frenette, Patrick Mehlen, Gerald de Haan, Nina Cabezas-Wallscheid, Andreas Trumpp
Summary: Haematopoietic stem cells are characterized by their self-renewal potential and dormancy. This study shows that niche-produced netrin-1 preserves HSC quiescence and self-renewal through neogenin-1, with a decline in netrin-1 production during aging leading to decreased Neo1-mediated HSC self-renewal.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Yang Han, Milos Nikolic, Michael Gobs, Julia Franzen, Gerald de Haan, Hartmut Geiger, Wolfgang Wagner
SCIENTIFIC REPORTS
(2020)
Article
Hematology
Arthur Flohr Svendsen, Daozheng Yang, KyungMok Kim, Seka Lazare, Natalia Skinder, Erik Zwart, Anna Mura-Meszaros, Albertina Ausema, Bjoern von Eyss, Gerald de Haan, Leonid Bystrykh
Summary: Despite heterogeneity between individual studies, a core and robust signature of transcriptional deregulation in aging murine hematopoietic stem cells (HSC) was identified, characterized by increased transcriptional activation and membrane-associated transcripts. Additionally, the presence of transcriptionally young-like HSCs in aged bone marrow was revealed through single-cell transcriptomics analysis.
Review
Cell Biology
Daozheng Yang, Gerald de Haan
Summary: Hematopoietic stem cells (HSCs) play a crucial role in lifelong blood cell production. Aging impacts HSC function, with inflammation emerging as a key factor in driving this process. Both intrinsic and extrinsic factors contribute to HSC aging.
Article
Cell Biology
Marlinde J. Smit, Tosca E. Martini, Inna Armandari, Irena Bockaj, Walderik W. Zomerman, Eduardo S. de Camargo Magalhaes, Zillah Siragna, Tiny G. J. Meeuwsen, Frank J. G. Scherpen, Mirthe H. Schoots, Martha Ritsema, Wilfred F. A. den Dunnen, Eelco W. Hoving, Judith T. M. L. Paridaen, Gerald de Haan, Victor Guryev, Sophia W. M. Bruggeman
Summary: Sonic hedgehog (SHH) medulloblastoma originates from the cerebellar granule neuron progenitor (CGNP) lineage and shows age-specific lesions. The developmental stage of CGNP plays a role in the age-specific aberrations observed in SHH tumors. Infant medulloblastoma and early embryonic CGNPs exhibit low primary cilium expression and reduced responsiveness to the upstream SHH pathway component Smoothened. Therefore, drugs targeting the downstream SHH pathway may be most suitable for infant medulloblastoma patients.
JOURNAL OF CELL SCIENCE
(2022)
Article
Multidisciplinary Sciences
Kyung Mok Kim, Anna Mura-Meszaros, Marie Tollot, Murali Shyam Krishnan, Marco Grundl, Laura Neubert, Marco Groth, Alejo Rodriguez-Fraticelli, Arthur Flohr Svendsen, Stefano Campaner, Nico Andreas, Thomas Kamradt, Steve Hoffmann, Fernando D. Camargo, Florian H. Heidel, Leonid Bystrykh, Gerald de Haan, Bjorn von Eyss
Summary: As individuals age, the immune system's function declines due to defects in hematopoietic stem cells (HSCs). Researchers have discovered that the Hippo pathway coactivator TAZ plays a crucial role in protecting aging HSCs from functional decline by buffering the loss of PU.1 activity, and have identified Clca3a1 as a marker for young-like HSCs even in old mice.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Paola Serrano Martinez, Martti Maimets, Reinier Bron, Ronald van Os, Gerald de Haan, Sarah Pringle, Robert P. Coppes
Summary: Stem/progenitor cells play a crucial role in maintaining salivary gland function and generating functional cells. However, there is limited understanding of stem/progenitor cells in the submandibular gland, particularly their contribution to adult gland homeostasis and the differences between embryonic and adult stem/progenitor cells. This study used a pulse-and-chase system to investigate potential stem/progenitor cells in the submandibular gland and found that label-retaining cells were mainly located in ductal or mesenchymal cells, rather than stem/progenitor cells. These label-retaining cells showed limited self-renewal ability, while non-label retaining cells exhibited differentiation and long-term expansion potential as organoids.
Article
Cell Biology
Ana Guerrero, Andrew J. Innes, Pierre-Francois Roux, Sonja C. Buisman, Johannes Jung, Laura Ortet, Victoria Moiseeva, Verena Wagner, Lucas Robinson, Albertina Ausema, Anna Potapova, Eusebio Perdiguero, Ellen Weersing, Marieke Aarts, Nadine Martin, Torsten Wuestefeld, Pura Munoz-Canoves, Gerald de Haan, Oliver Bischof, Jesus Gil
Summary: 3-Deazaadenosine (3DA) is a promising drug that enhances the efficiency of cellular therapies by restraining senescence.
