Review
Immunology
Francesca Matteini, Medhanie A. Mulaw, M. Carolina Florian
Summary: The aging of the bone marrow niche leads to declining HSC function, but certain niche structures and signals are crucial for maintaining HSC function. The use of new technical tools has revealed the impact of BM niche aging on HSCs.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Engineering, Biomedical
Victoria Barnhouse, Nathan Petrikas, Cody Crosby, Janet Zoldan, Brendan Harley
Summary: The study developed and characterized a three-dimensional perivascular tissue model to investigate the influence of the perivascular secretome on HSC behavior, finding that perivascular conditioned media promoted maintenance of a greater fraction of hematopoietic stem and progenitor cells within a 4-day culture period.
ANNALS OF BIOMEDICAL ENGINEERING
(2021)
Article
Cell Biology
Yutian Chen, Qiang Pu, Yongyuan Ma, Hua Zhang, Tinghong Ye, Chengjian Zhao, Xiaojuan Huang, Yafeng Ren, Lina Qiao, Han-Min Liu, Charles T. Esmon, Bi-Sen Ding, Zhongwei Cao
Summary: Aging impairs regenerative capacity and leads to fibrosis in organs. Aberrant reprogramming of hematopoietic and vascular cell crosstalk in aging hinders regeneration and promotes fibrosis. Targeting aberrant endothelial node molecules may facilitate regeneration without scarring in the repair of multiple organs.
Review
Medicine, Research & Experimental
Yangdan Liu, Chiakang Ho, Dongsheng Wen, Jiaming Sun, Lu Huang, Ya Gao, Qingfeng Li, Yifan Zhang
Summary: The self-renewal ability of stem cells is crucial for skin homeostasis, aging, and wound repair. COL17, as a component of the stem cell niche, plays a pivotal role in regulating stem cell maintenance and function.
Article
Hematology
Alice Tang, Ana Nicolle Strat, Mahmudur Rahman, Helen Zhang, Weili Bao, Yunfeng Liu, David Shi, Xiuli An, Deepa Manwani, Patricia Shi, Karina Yazdanbakhsh, Avital Mendelson
Summary: Studies have found that murine SCD MSCs exhibit altered gene signatures, reduced stem cell properties, and increased oxidative stress, leading to decreased HSC maintenance ability. The activation of Toll-like receptor-4 through p65 in MSCs further exacerbates MSC dysfunction in SCD.
Review
Cell Biology
Julia Froebel, Theresa Landspersky, Guelce Percin, Christina Schreck, Susann Rahmig, Alessandro Ori, Daniel Nowak, Marieke Essers, Claudia Waskow, Robert A. J. Oostendorp
Summary: The bone marrow environment, known as the niche, plays a vital role in maintaining blood cell formation throughout life. Different types of stress can disrupt the niche, leading to deregulation of hematopoietic stem cells and their function. Both acute and chronic insults can alter the cellular composition and structure of the niche, ultimately affecting hematopoiesis and increasing susceptibility to diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
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 & 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
Biochemistry & Molecular Biology
Zhe Chen, Qian Guo, Guanbin Song, Yu Hou
Summary: Hematopoietic stem cells (HSCs) remain dormant in a cell-cycle quiescence state to maintain their self-renewal capacity and play a crucial role in hematopoietic system homeostasis. Dysregulation of quiescence can lead to HSC dysfunction and result in abnormal hematopoiesis and leukemia transformation. Intrinsic molecular networks and extrinsic signals regulate HSC quiescence, and cell metabolism drives the transition between quiescence and activation of HSCs. Investigating the complex regulatory networks of HSC quiescence expands our understanding of blood cell formation and has clinical implications.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Cell Biology
Steicy Sobrino, Alessandra Magnani, Michaela Semeraro, Loredana Martignetti, Akira Cortal, Adeline Denis, Chloe Couzin, Capucine Picard, Jacinta Bustamante, Elisa Magrin, Laure Joseph, Cecile Roudaut, Aurelie Gabrion, Tayebeh Soheili, Corinne Cordier, Olivier Lortholary, Francois Lefrere, Frederic Rieux-Laucat, Jean-Laurent Casanova, Sylvain Bodard, Nathalie Boddaert, Adrian J. Thrasher, Fabien Touzot, Sophie Taque, Felipe Suarez, Ambroise Marcais, Agathe Guilloux, Chantal Lagresle-Peyrou, Anne Galy, Antonio Rausell, Stephane Blanche, Marina Cavazzana, Emmanuelle Six
Summary: X-linked chronic granulomatous disease (CGD) is a serious condition associated with defective phagocytosis, infections, and inflammatory complications. A clinical trial of lentivirus-based gene therapy was conducted on four patients, showing successful engraftment and clinical benefits in two patients, while the other two experienced loss of gene-corrected cells. Single-cell transcriptomic analysis revealed lower levels of hematopoietic stem cells (HSCs) in CGD patients, especially in those with poor engraftment. Aberrant HSC state and elevated interferon genes were identified as predictors of HSC engraftment failure.
CELL REPORTS MEDICINE
(2023)
Review
Cell Biology
Yan Man, Xiangmei Yao, Tonghua Yang, Yajie Wang
Summary: The self-renewal and differentiation of hematopoietic stem cells are tightly controlled by various cells and cytokines in the bone marrow microenvironment. Changes in the niche composition can lead to hematological malignancies, and processes like homing, proliferation, and differentiation of HSCs are crucial for the success of hematopoietic stem cell transplantation. Single-cell sequencing and in vivo imaging are powerful tools for studying the bone marrow microenvironment in diseases like leukemia and after transplantation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Cornelia Lee-Thedieck, Peter Schertl, Gerd Klein
Summary: This review provides a comprehensive overview of the extracellular matrix (ECM) in hematopoietic stem cell (HSC) niches and highlights its importance in regulating cellular function and niche structure. The role of different classes of ECM molecules and their interactions with cells are discussed, along with the significance of matrix remodeling and biophysics in HSC niche function. The review also examines the application of current knowledge of ECM in artificial HSC niches for HSC expansion, targeted differentiation, and drug testing.
ADVANCED DRUG DELIVERY REVIEWS
(2022)
Article
Multidisciplinary Sciences
Runfeng Miao, Harim Chun, Xing Feng, Ana Cordeiro Gomes, Jungmin Choi, Joao P. Pereira
Summary: This study reveals that a complex homeostatic balance between hematopoietic stem cells (HSCs) and hematopoietic progenitor cells is maintained through competition for a limited amount of cell signaling molecule. When early hematopoietic progenitors fail to interact with specific cells, HSC numbers increase.
NATURE COMMUNICATIONS
(2022)
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.
Editorial Material
Cell Biology
Kaosheng Lv, Wei Tong
Summary: The novel role of Bmi1 in regulating ribosome biogenesis and protein synthesis in hematopoietic stem cells has been discovered. Bmi1 is essential for maintaining HSCs, and its deficiency leads to reduced transplantability and protein stress.
GENES & DEVELOPMENT
(2022)
Meeting Abstract
Hematology
Qiqi Lin, Srinivas Chatla, Limei Wu, Fabliha Chowdhury, Wei Du
Article
Hematology
Xue Li, Srinivas Chatla, Andrew F. Wilson, Limei Wu, Neha Atale, Wei Du
Summary: Our study reveals the important role of TREM1 in leukemogenesis. Selective deletion of Trem1 in the hematopoietic compartment reduces the leukemogenic activity of leukemia stem cells. Trem1 expression is associated with DNA damage, oncogenic stress, and inflammatory signature. Inhibiting Trem1 inflammatory responses can reduce the proliferation of leukemia stem cells.
Review
Immunology
Lei Gao, Anqi Zhang, Fuyuan Yang, Wei Du
Summary: Neoantigens, abnormal proteins produced by genetic mutations, have immunogenicity and represent specific targets for precision immunotherapy. Neoantigen vaccines and adoptive cell therapy targeting neoantigens have become research hotspots in the treatment of head and neck squamous cell carcinoma (HNSCC). This paper reviews recent trials related to neoantigen vaccine treatments for HNSCC, introduces adoptive cell therapy targeting neoantigens, and discusses the potential of neoantigens in HNSCC treatment.
Meeting Abstract
Hematology
Limei Wu, Qiqi Lin, Srinivas Chatla, Neha Atale, Zhenxia J. Gao, Jonathan Joseph, Emily Wolff, Wei Du
Article
Oncology
Konstantin Golovine, Gleb Abalakov, Zhaorui Lian, Srinivas Chatla, Adam Karami, Kumaraswamy Naidu Chitrala, Jozef Madzo, Margaret Nieborowska-Skorska, Jian Huang, Tomasz Skorski
Summary: This study found that ABL1 kinase plays a tumor suppressor role in hematological malignancies carrying AML1-ETO and NUP98-PMX1 fusion proteins. ABL1-deficient cells showed a proliferation advantage, while overexpression and pharmacological stimulation of ABL1 kinase led to reduced proliferation. The study identified PI3K signaling as a dominant mechanism contributing to growth factor independence in ABL1-deficient cells.
BLOOD CANCER JOURNAL
(2023)
Article
Hematology
Umeshkumar Vekariya, Monika Toma, Margaret Nieborowska-Skorska, Bac Viet Le, Marie-Christine Caron, Anna-Mariya Kukuyan, Katherine Sullivan-Reed, Paulina Podszywalow-Bartnicka, Kumaraswamy N. Chitrala, Jessica Atkins, Malgorzata Drzewiecka, Wanjuan Feng, Joe Chan, Srinivas Chatla, Konstantin Golovine, Jaroslav Jelinek, Tomasz Sliwinski, Jayashri Ghosh, Ksenia Matlawska-Wasowska, Gurushankar Chandramouly, Reza Nejati, Mariusz Wasik, Stephen M. Sykes, Katarzyna Piwocka, Emir Hadzijusufovic, Peter Valent, Richard T. Pomerantz, George Morton, Wayne Childers, Huaqing Zhao, Elisabeth M. Paietta, Ross L. Levine, Martin S. Tallman, Hugo F. Fernandez, Mark R. Litzow, Gaorav P. Gupta, Jean-Yves Masson, Tomasz Skorski
Summary: Leukemia cells accumulate DNA damage, but altered DNA repair mechanisms protect them from apoptosis. Formaldehyde generated by serine/1-carbon cycle metabolism contributes to the accumulation of toxic DNA-protein crosslinks (DPCs) in leukemia cells. Oncogenic tyrosine kinases (OTKs) enhance the expression of DNA polymerase theta (POL theta) to repair DPC-containing DNA double-strand breaks. Inhibition of POL theta can be an effective therapeutic strategy for leukemia.
Article
Medicine, Research & Experimental
Qiqi Lin, Limei Wu, Srinivas Chatla, Fabliha A. Chowdhury, Neha Atale, Jonathan Joseph, Wei Du
Summary: The crosstalk between the BM microenvironment and HSCs is critical for HSC regeneration. Deletion of the FA genes Fanco and Fancc dampened HSC regeneration and FA HSCs showed persistent upregulation of Prox1. The paracrine Wnt5a/Prox1 signaling axis regulates HSC regeneration under conditions of injury and aging.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
