Article
Immunology
Siddharth Krishnan, Kelly Wemyss, Ian E. Prise, Flora A. McClure, Conor O'Boyle, Hayley M. Bridgeman, Tovah N. Shaw, John R. Grainger, Joanne E. Konkel
Summary: HSPCs were found to reside and differentiate in healthy gingiva, a key oral barrier. Gingival HSPCs exhibited similar characteristics to bone marrow HSPCs but responded differently to inflammatory insults, only responding to oral rather than systemic inflammation.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Araceli Aparecida Hastreiter, Guilherme G. dos Santos, Edson Naoto Makiyama, Ed Wilson Cavalcante Santos, Primavera Borelli, Ricardo Ambrosio Fock
Summary: Protein malnutrition alters the synthesis of specific growth factors and cytokines by mesenchymal stem cells, leading to the impairment of hematopoietic stem cells and hematopoietic progenitors. This study demonstrates for the first time the role of mesenchymal stem cells in regulating hematopoietic cells under protein malnutrition conditions.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2021)
Article
Cell Biology
Steven J. Greco, Seda Ayer, Khadidiatou Guiro, Garima Sinha, Robert J. Donnelly, Markos H. El-Far, Lauren S. Sherman, Yannick Kenfack, Sri Harika Pamarthi, Marina Gergues, Oleta A. Sandiford, Michael J. Schonning, Jean -Pierre Etchegaray, Pranela Rameshwar
Summary: This study demonstrates the potential to reverse age-associated morbidity by restoring the aged hematopoietic system using miRNA cargo to target specific genes. By introducing restorative miRs in aged cells, improvements in aged hallmarks such as altered lymphoid:myeloid ratio, decreased inflammation, and cellular senescence were observed. Additionally, the study found that natural killer cells can eliminate dormant breast cancer cells in vivo, indicating the broad relevance of this approach in preventing and reversing age-associated disorders.
Review
Endocrinology & Metabolism
Ziru Li, Clifford J. Rosen
Summary: Bone marrow adipose tissue (BMAT) is a significant component of the bone marrow space in healthy adults, but its expansion is associated with aging, obesity, anorexia nervosa, and irradiation. While traditionally viewed as a negative component, recent studies have revealed that BMAT can serve as an energy reservoir and also plays a role in regulating bone formation and hematopoiesis. This review summarizes the unique characteristics of BMAT and provides an updated understanding of its physiological roles based on a newly established mouse model.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(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
Cell Biology
Annamaria Aprile, Laura Raggi, Simona Bolamperti, Isabella Villa, Mariangela Storto, Gaia Morello, Sarah Marktel, Claudio Tripodo, Maria Domenica Cappellini, Irene Motta, Alessandro Rubinacci, Giuliana Ferrari
Summary: Clinical evidence suggests a relationship between blood and bone, but the underlying mechanism is not fully understood. A study using beta-thalassemia as a model found that increased fibroblast growth factor 23 (FGF23) levels in patients and mice with beta-thalassemia were induced by erythropoietin via ERK1/2 and STAT5 pathways. Inhibiting FGF23 signaling with carboxyl-terminal FGF23 peptide rescued bone defects and restored hematopoietic stem cell function in mice with beta-thalassemia. FGF23 may serve as a molecular link connecting anemia, bone, and the hematopoietic stem cell niche.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Annamaria Aprile, Laura Raggi, Simona Bolamperti, Isabella Villa, Mariangela Storto, Gaia Morello, Sarah Marktel, Claudio Tripodo, Maria Domenica Cappellini, Irene Motta, Alessandro Rubinacci, Giuliana Ferrari
Summary: This study demonstrates the overproduction of fibroblast growth factor 23 (FGF23) in patients and mice with beta-thalassemia, and shows that inhibition of FGF23 signaling is a safe and effective therapeutic strategy to rescue bone defects and restore hematopoietic stem cell function. FGF23 may serve as a molecular link connecting anemia, bone, and the HSC niche.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Biotechnology & Applied Microbiology
Azmeer Sharipol, Maggie L. Lesch, Celia A. Soto, Benjamin J. Frisch
Summary: This study developed a modular murine bone marrow microenvironment-on-chip that can maintain functional hematopoietic stem cells in vitro. The chip model has a better representation of the human bone marrow, which contributes to a deeper understanding of bone marrow pathophysiology.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Olga Perik-Zavodskaia, Roman Perik-Zavodskii, Kirill Nazarov, Marina Volynets, Saleh Alrhmoun, Julia Shevchenko, Sergey Sennikov
Summary: This study comprehensively characterized mouse erythroid cells using transcriptomic and proteomic approaches, revealing functional differences and gene expression profiles. It highlights the importance of investigating specific markers and subpopulations of erythroid cells in future studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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
Biology
Virginia Folgado-Marco, Kristina Ames, Jacky Chuen, Kira Gritsman, Nicholas E. Baker
Summary: A conditional knockout mouse was generated by partially deleting Rps12. Mice inheriting the Rps12(KO/+) genotype exhibited growth and morphological defects, pancytopenia, and impaired erythropoiesis. There was a significant reduction in hematopoietic stem cells and progenitors in the bone marrow of Rps12(KO/+) mice.
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)
Article
Cell & Tissue Engineering
Gordian Born, Marina Nikolova, Arnaud Scherberich, Barbara Treutlein, Andres Garcia-Garcia, Ivan Martin
Summary: The study suggests using stromal vascular fraction derived from human adipose tissue to vascularize 3D osteoblastic bone marrow niches, leading to improved maintenance of HSCs and increased CFU-GEMM numbers. Vascularization also positively affects osteogenic gene expression in the niche.
JOURNAL OF TISSUE ENGINEERING
(2021)
Review
Immunology
Alice Pievani, Roberto Savoldelli, Juliane Poelchen, Elisa Mattioli, Giorgio Anselmi, Alice Girardot, Jochen Utikal, Pierre Bourdely, Marta Serafini, Pierre Guermonprez
Summary: Tissue engineering provides numerous opportunities in regenerative medicine, drug testing, and modeling hematopoiesis. Replicating the physiological microenvironments supporting leukocyte development is crucial for accurately modeling immune cell development. Immune niches are characterized by mesenchymal stromal cells that play unique roles in organizing niche development, maintenance, and function.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Yeojin Lee, Juliana Leslie, Ying Yang, Lei Ding
Summary: This study reveals the cellular composition and mechanism of hematopoietic stem cell (HSC) niche formation in the developing liver. Endothelial cells and hepatic stellate cells create a perisinusoidal vascular niche for HSC development by producing stem cell factor (SCF).
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Hematology
Anne Korporaal, Nynke Gillemans, Steven Heshusius, Ileana Cantu, Emile van den Akker, Thamar B. van Dijk, Marieke von Lindern, Sjaak Philipsen
Summary: Haploinsufficiency of transcription factor KLF1 leads to various erythroid phenotypes; the mouse Nan strain carrying the Klf1(Nan) variant affects globin expression patterns during development; different KLF1 variants have variant-specific impacts on the expression of embryonic/fetal globin genes.
Article
Cell & Tissue Engineering
Cathelijn E. M. Aarts, Eszter Varga, Steven Webbers, Judy Geissler, Marieke von Lindern, Taco W. Kuijpers, Emile van den Akker
Summary: Induced pluripotent stem cell line generated from erythroblasts of a patient with severe congenital neutropenia can be used to study the disease and the role of neutrophil elastase protein.
STEM CELL RESEARCH
(2021)
Article
Cell & Tissue Engineering
Cathelijn E. M. Aarts, Eszter Varga, Steven Webbers, Judy Geissler, Marieke von Lindern, Taco W. Kuijpers, Emile van den Akker
Summary: The generated iPSCs from EBLs of a CHS patient can be utilized to study the pathophysiology of CHS and the role of LYST in different cell types. The iPSCs showed a normal karyotype and expression of pluripotency associated markers, along with the ability to spontaneously differentiate towards the three germ layers in vitro.
STEM CELL RESEARCH
(2021)
Article
Cell & Tissue Engineering
Cathelijn E. M. Aarts, Eszter Varga, Steven Webbers, Judy Geissler, Marieke von Lindern, Taco W. Kuijpers, Emile van den Akker
Summary: This study successfully generated induced pluripotent stem cells from erythroblasts of a patient with Gray Platelet Syndrome, providing a new tool for further research on the pathophysiology of the disease and the basic functions of the NBEAL2 protein in different cell types.
STEM CELL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Alexander Mattebo, Taha Sen, Maria Jassinskaja, Kristyna Pimkova, Isabel Prieto Gonzalez-Albo, Abdul Ghani Alattar, Ramprasad Ramakrishnan, Stefan Lang, Marcus Jaras, Jenny Hansson, Shamit Soneji, Sofie Singbrant, Emile van den Akker, Johan Flygare
Summary: YPEL family genes are highly conserved and potentially involved in essential cellular processes. Ypel4, specifically expressed in late terminal erythroid differentiation, plays a role in maintaining normal red cell membrane integrity. Ypel4-null mice exhibit secondary polycythemia and intrinsic defects in red blood cells.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Jesse Eernstman, Barbera Veldhuisen, Peter Ligthart, Marieke von Lindern, Ellen van der Schoot, Emile van den Akker
Summary: Beta-hemoglobinopathies are differentiated after birth by a switch to mutated beta-globin, while haploinsufficiency of the erythroid-specific transcription factor KLF1 is correlated with high persistence of fetal hemoglobin (HPFH). Screening 55 Lutheran weak or negative donors revealed KLF1 variants in 80% of negative donors, including 13 different variants and 6 novel ones. KLF1 plays a crucial role in regulating the expression of CD44, Lu, and HbF during erythropoiesis.
SCIENTIFIC REPORTS
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Thomas Blom, Rutger Meinsma, Franca di Summa, Emile van den Akker, Andre B. P. van Kuilenburg, Marten Hansen, Godelieve A. M. Tytgat
Summary: The study found that human megakaryocytes cultured in vitro can selectively uptake MIBG, and the selective serotonin reuptake inhibitor citalopram can inhibit the uptake of MIBG. This research provides a promising strategy of concomitant administration of citalopram during [I-131]MIBG therapy to prevent thrombocytopenia.
Letter
Hematology
Daniel Flormann, Min Qiao, Nicoletta Murciano, Giulia Iacono, Alexis Darras, Sebastian Hof, Steffen M. Recktenwald, Maria Giustina Rotordam, Nadine Becker, Juergen Geisel, Christian Wagner, Marieke von Lindern, Emile van den Akker, Lars Kaestner
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Article
Multidisciplinary Sciences
Steven Heshusius, Laura Grech, Nynke Gillemans, Rutger W. W. Brouwer, Xander T. den Dekker, Wilfred F. J. van IJcken, Benjamin Nota, Alex E. Felice, Thamar B. van Dijk, Marieke von Lindern, Joseph Borg, Emile van den Akker, Sjaak Philipsen
Summary: Haploinsufficiency of KLF1 gene is associated with hereditary persistence of fetal hemoglobin. Decreasing the activity of KLF1 has been proposed as a potential therapeutic strategy for beta-hemoglobinopathies. However, individuals with the same KLF1 variant in the same family show a wide range of HbF levels, which cannot be explained by co-inheritance of known HbF-modulating variants. Studying erythroid progenitors, researchers find that variation in expression of the wildtype KLF1 allele may explain a significant part of the variability in HbF levels observed in KLF1 haploinsufficiency. These findings have implications for the understanding of haploinsufficiency phenotypes and the pathogenicity of variants in other transcriptional regulators.
SCIENTIFIC REPORTS
(2022)
Article
Hematology
Marjon H. Cnossen, Iris van Moort, Simone H. Reitsma, Moniek P. M. de Maat, Roger E. G. Schutgens, Rolf T. Urbanus, Hester F. Lingsma, Ron A. A. Mathot, Samantha C. Gouw, Karina Meijer, Annelien L. Bredenoord, Rieke van der Graaf, Karin Fijnvandraat, Alexander B. Meijer, Emile van den Akker, Ruben Bierings, Jeroen C. J. Eikenboom, Maartje van den Biggelaar, Masja de Haas, Jan Voorberg, Frank W. G. Leebeek
Summary: The SYMPHONY consortium aims to personalize treatment for patients with an inborn bleeding disorder by understanding the mechanisms behind interindividual variations in bleeding phenotype. The consortium will investigate both diagnosed and undiagnosed patients and will focus on diagnosis, treatment, and fundamental research. Collaboration between patients and researchers from different areas of expertise is expected to enhance the impact of the consortium.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Cell Biology
Greta Simionato, Antonia Rabe, Joan Sebastian Gallego-Murillo, Carmen van der Zwaan, Arie Johan Hoogendijk, Maartje van den Biggelaar, Giampaolo Minetti, Anna Bogdanova, Heimo Mairbaurl, Christian Wagner, Lars Kaestner, Emile van den Akker
Summary: Research indicates that erythroid maturation is accelerated under low oxygen conditions, with a more concave morphology observed. Hematopoietic stem and progenitor cells affected by hypoxia at high altitude show strong adaptability during in vitro erythropoiesis.
Article
Biotechnology & Applied Microbiology
Joan Sebastian Gallego-Murillo, Giulia Iacono, Luuk A. M. van der Wielen, Emile van den Akker, Marieke von Lindern, Sebastian Aljoscha Wahl
Summary: This study reports on the scale-up of cRBC production from static cultures to 3 L stirred tank bioreactors, and identifies the effect of operating conditions on the efficiency of the process.
BIOTECHNOLOGY AND BIOENGINEERING
(2022)
Article
Genetics & Heredity
Han J. M. P. Verhagen, Carlijn Kuijk, Laurens Rutgers, Anne M. Kokke, Santhe A. van der Meulen, Gerard van Mierlo, Carlijn Voermans, Emile van den Akker
Summary: This study evaluated the efficiency of gene editing using RNPs in human HSPCs and found that gRNA design is critical. In silico prediction models were ineffective, but a new in vitro transcribed gRNA screening model was established. RNP-based screening outperformed prediction models, and gene editing was equally efficient in different HSPC subpopulations.
Article
Multidisciplinary Sciences
Joan Sebastian Gallego-Murillo, Nurcan Yagci, Eduardo Machado Pinho, Sebastian Aljoscha Wahl, Emile van den Akker, Marieke von Lindern
Summary: Deferiprone, a cell membrane-permeable drug, can replace holotransferrin as an iron carrier in red blood cell cultures, reducing the cost and improving the economic viability of large-scale production.
SCIENTIFIC REPORTS
(2023)
Article
Hematology
Marea V. E. van der Rijst, Asena Abay, Francesca Aglialoro, C. Ellen van der Schoot, Emile van den Akker
Summary: The study investigated the impact of SMIM1 mutations on erythrocyte Vel expression, finding that the mutations do not affect SMIM1 membrane expression during cellular differentiation, but may have a dominant negative effect on Vel expression during erythrocyte maturation.