Article
Cell Biology
Jia Hao, Hao Zhou, Kristen Nemes, Daniel Yen, Winfield Zhao, Charles Bramlett, Bowen Wang, Rong Lu, Keyue Shen
Summary: This research demonstrates that membrane-bound factors play a unique role in regulating stem cell morphology and function, uncovering the signaling mechanism involved in the interaction between hematopoietic stem cells and niche stromal cells.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
S. S. Hoepner, Ana Raykova, R. Radpour, M. A. Amrein, D. Koller, G. M. Baerlocher, C. Riether, A. F. Ochsenbein
Summary: The study demonstrates that LIGHT and its receptor LT beta R promote quiescence and self-renewal of HSCs, while LT beta R deficiency contributes to survival in a mouse leukemia model.
NATURE COMMUNICATIONS
(2021)
Article
Engineering, Biomedical
Wenjing Li, Haiwei Liang, Yanxiao Ao, Baixue Tang, Junyang Li, Ning Li, Jianwei Wang, Yanan Du
Summary: Hematopoietic stem cells (HSCs) have the ability to differentiate into all blood cells and immune cells. By simulating the bone marrow microenvironment, we designed degradable scaffolds to regulate the fate of HSCs. In vivo transplantation confirmed the importance of the scaffolds in maintaining hematopoietic function, providing a foundation for parameter design in 3D HSC culture systems.
Review
Hematology
Vincenzo Calvanese, Hanna K. A. Mikkola
Summary: Developmental hematopoiesis is a complex process involving the generation of differentiated blood cells and the establishment of a pool of undifferentiated hematopoietic stem cells (HSCs) for postnatal life. Recent single-cell studies have identified rare human HSCs and traced their origin to a unique type of arterial endothelium in the aorta-gonad-mesonephros region. These studies provide new insights into HSC generation and may inform efforts to generate HSCs from pluripotent stem cells in vitro.
Article
Immunology
Giovanni Cova, Chiara Taroni, Marie-Celin Deau, Qi Cai, Vincent Mittelheisser, Muriel Philipps, Matthieu Jung, Marie Cerciat, Stephanie Le Gras, Christelle Thibault-Carpentier, Bernard Jost, Leif Carlsson, M. Angela Thornton, M. Ethan Shevach, Peggy Kirstetter, Philippe Kastner, Susan Chan
Summary: The transcription factor Helios plays a crucial role in suppressing the megakaryocyte lineage and maintaining pluripotency of hematopoietic stem cells in mice. Its absence leads to bias towards megakaryocyte lineage and partial resemblance to cells of aging animals, indicating the importance of negative and positive priming events in lineage commitment.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Cell Biology
Diego A. Lopez, April C. Apostol, Eric J. Lebish, Clint H. Valencia, Mari Carmen Romero-Mulero, Polina Pavlovich, Gloria E. Hernandez, E. Camilla Forsberg, Nina Cabezas-Wallscheid, Anna E. Beaudin
Summary: Adult hematopoietic stem and progenitor cells respond to inflammation and infection, and fetal hematopoietic stem and progenitor cells also respond to prenatal inflammation, shaping post-natal hematopoiesis and immune cell function. Maternal immune activation causes diverse responses in fetal hematopoietic stem and progenitor cells, including changes in quiescence, expansion, and lineage-biased output.
Review
Cell Biology
Bai Ling, Yunyang Xu, Siyuan Qian, Ze Xiang, Shihai Xuan, Jian Wu
Summary: Hematopoietic stem cells (HSCs) play a crucial role in the hematopoietic system as they can self-renew and differentiate into various blood cells. The mTOR signaling pathway is an important regulator of HSCs' differentiation, self-renewal, and quiescence, and several molecules can modulate these potentials by influencing this pathway. This review discusses the regulation of HSCs' three potentials by the mTOR signaling pathway and highlights potential regulators. Additionally, the clinical significance of studying this regulation and future predictions are also outlined.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell & Tissue Engineering
Angela Picerno, Francesca Giannuzzi, Claudia Curci, Giuseppe De Palma, Maria Giovanna Di Chiano, Simona Simone, Rossana Franzin, Anna Gallone, Vito Francesco Di Lorenzo, Alessandra Stasi, Giovanni Battista Pertosa, Carlo Sabba, Loreto Gesualdo, Fabio Sallustio
Summary: The lncRNA HOTAIR is highly expressed in renal progenitor cells and plays a key role in maintaining their proliferative capacity and limiting apoptosis. Knockout of HOTAIR leads to senescence of renal progenitor cells and decreased expression of the stem cell marker CD133. HOTAIR exerts its function through epigenetic silencing of cell cycle inhibitor p15.
Review
Oncology
Isabella Maria Mayer, Andrea Hoelbl-Kovacic, Veronika Sexl, Eszter Doma
Summary: Transplantation of adult hematopoietic stem cells is crucial for treating hematological disorders, while leukemic stem cells play a significant role in disease initiation and relapse. Understanding methods to maintain and expand hematopoietic cells, as well as isolate and enrich hematopoietic stem cells and leukemic stem cells, is essential for developing therapeutic strategies.
Article
Medicine, Research & Experimental
Yandan Chen, Shuyi Fang, Qingwei Ding, Rongzhen Jiang, Jiefeng He, Qin Wang, Yuting Jin, Xinxin Huang, Sheng Liu, Maegan L. Capitano, Thao Trinh, Yincheng Teng, Qingyou Meng, Jun Wan, Hal E. Broxmeyer, Bin Guo
Summary: The study found that under ex vivo culturing conditions, HSCs with low levels of mitochondrial ROS were enriched in the CD34+CD133+ADGRG1+ CB cell population. These cells showed increased mitochondrial oxidative stress in transcriptomic and metabolic profiling, along with loss of stemness.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Cell Biology
In-Chi Young, Bogang Wu, Jaclyn Andricovich, Sung-Ting Chuang, Rong Li, Alexandros Tzatsos, Ray-Chang Wu, Mei-Yi Wu
Summary: ARID4B interferes with KITLG/KIT signaling, promoting HSC differentiation instead of self-renewal. ARID4B-deficient HSCs self-express KITLG and overexpress KIT, leading to differentiation. Inhibition of Src family kinases rescues the HSC differentiation defect caused by ARID4B loss.
Article
Cell & Tissue Engineering
Chuti Laowtammathron, Chanchao Lorthongpanich, Nittaya Jiamvoraphong, Pimonwan Srisook, Phatchanat Klaihmon, Pakpoom Kheolamai, Sudjit Luanpitpong, Surapol Issaragrisil
Summary: The study explores the role of YAP in hematopoietic differentiation of hiPSCs. It is found that suppressing YAP activity enhances the efficiency of hematopoietic differentiation and increases the yield of HSPCs.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Cell & Tissue Engineering
Hector Huerga Encabo, Iker Valle Aramburu, Manuel Garcia-Albornoz, Marion Piganeau, Henry Wood, Anna Song, Alessandra Ferrelli, Aneesh Sharma, Carlos M. Minutti, Marie-Charlotte Domart, Despoina Papazoglou, Kristian Gurashi, Miriam Llorian Sopena, Robert Goldstone, Todd Fallesen, Qian Wang, Linda Ariza-McNaughton, Daniel H. Wiseman, Kiran Batta, Rajeev Gupta, Venizelos Papayannopoulos, Dominique Bonnet
Summary: Somatic mutations in hematopoietic stem cells (HSCs) can lead to clonal hematopoiesis (CH) and the production of mutated immune cells, increasing the risk of leukemia and inflammatory diseases. Through genetic engineering and transplantation, researchers found that loss of the TET2 gene in human HSCs resulted in abnormal development and function of neutrophils, leading to heightened inflammatory responses and compact chromatin structure. These findings provide insights into detecting TET2-CH and preventing CH-associated pathologies mediated by neutrophil extracellular traps (NET).
Article
Biochemistry & Molecular Biology
James L. C. Che, Daniel Bode, Iwo Kucinski, Alyssa H. Cull, Fiona Bain, Hans J. Becker, Maria Jassinskaja, Melania Barile, Grace Boyd, Miriam Belmonte, Andy G. X. Zeng, Kyomi J. Igarashi, Juan Rubio-Lara, Mairi S. Shepherd, Anna Clay, John E. Dick, Adam C. Wilkinson, Hiromitsu Nakauchi, Satoshi Yamazaki, Berthold Gottgens, David G. Kent
Summary: The use of Fgd5 reporter mouse and EPCR surface marker allows for the exclusive identification of HSCs from non-HSCs in expansion cultures, revealing a gene expression signature that can identify functional HSCs from multiple cellular states.
Article
Oncology
Elzbieta Karnas, Malgorzata Sekula-Stryjewska, Katarzyna Kmiotek-Wasylewska, Sylwia Bobis-Wozowicz, Damian Ryszawy, Michal Sarna, Zbigniew Madeja, Ewa K. Zuba-Surma
Summary: By treating CB-HSPCs with hiPSC-EVs, the functional properties of CB-HSPCs, including metabolism, hematopoietic and clonogenic potential, can be enhanced, as well as improving their homing and engraftment capacity in vivo.
Article
Medicine, General & Internal
Amelia Green, Helen Curtis, William Hulme, Elizabeth Williamson, Helen McDonald, Krishnan Bhaskaran, Christopher Rentsch, Anna Schultze, Brian MacKenna, Viyaasan Mahalingasivam, Laurie Tomlinson, Alex Walker, Louis Fisher, Jon Massey, Colm Andrews, Lisa Hopcroft, Caroline Morton, Richard Croker, Jessica Morley, Amir Mehrkar, Seb Bacon, David Evans, Peter Inglesby, George Hickman, Tom Ward, Simon Davy, Rohini Mathur, John Tazare, Rosalind Eggo, Kevin Wing, Angel Wong, Harriet Forbes, Chris Bates, Jonathan Cockburn, John Parry, Frank Hester, Sam Harper, Ian Douglas, Stephen Evans, Liam Smeeth, Ben Goldacre
Summary: While the majority of COVID-19 vaccine breakthrough cases in England were mild, some differences in rates of breakthrough cases have been identified in several clinical groups. Further analysis is needed to assess vaccine waning and rates of breakthrough COVID-19 between different variants in order to identify individuals at higher risk.
Article
Oncology
Grant D. Stewart, Sarah J. Welsh, Stephan Ursprung, Ferdia A. Gallagher, James O. Jones, Jacqui Shields, Christopher G. Smith, Thomas J. Mitchell, Anne Y. Warren, Axel Bex, Ekaterini Boleti, Jade Carruthers, Tim Eisen, Kate Fife, Abdel Hamid, Alexander Laird, Steve Leung, Jahangeer Malik, Iosif A. Mendichovszky, Faiz Mumtaz, Grenville Oades, Andrew N. Priest, Antony C. P. Riddick, Balaji Venugopal, Michelle Welsh, Kathleen Riddle, Lisa E. M. Hopcroft, Robert J. Jones
Summary: The study demonstrates that axitinib can reduce the level of VTT in patients, leading to a reduction in the extent of surgery for a significant proportion of patients. However, some patients show poor response to axitinib.
BRITISH JOURNAL OF CANCER
(2022)
Letter
Dermatology
John R. P. Knight, Christopher G. Proud, Giovanna Mallucci, Tobias von der Haar, C. Mark Smales, Anne E. Willis, Owen J. Sansom
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Multidisciplinary Sciences
Maria Azkanaz, Bernat Corominas-Murtra, Saskia I. J. Ellenbroek, Lotte Bruens, Anna T. Webb, Dimitrios Laskaris, Koen C. Oost, Simona J. A. Lafirenze, Karl Annusver, Hendrik A. Messal, Sharif Iqbal, Dustin J. Flanagan, David J. Huels, Felipe Rojas-Rodriguez, Miguel Vizoso, Maria Kasper, Owen J. Sansom, Hugo J. Snippert, Prisca Liberali, Benjamin D. Simons, Pekka Katajisto, Edouard Hannezo, Jacco van Rheenen
Summary: The number and behavior of stem cells vary along the intestinal tract, with small intestines having twice as many effective stem cells as large intestines. This difference is attributed to the presence of retrograde cellular movement in small intestines, which allows cells positioned away from the crypt base to function as long-term effective stem cells.
Article
Biochemistry & Molecular Biology
Victor H. Villar, Maria Francesca Allega, Ruhi Deshmukh, Tobias Ackermann, Mark A. Nakasone, Johan Vande Voorde, Thomas M. Drake, Janina Oetjen, Algernon Bloom, Colin Nixon, Miryam Muller, Stephanie May, Ee Hong Tan, Lars Vereecke, Maude Jans, Gillian Blancke, Daniel J. Murphy, Danny T. Huang, David Y. Lewis, Thomas G. Bird, Owen J. Sansom, Karen Blyth, David Sumpton, Saverio Tardito
Summary: This study reveals that glutamine synthetase (GS) can produce a methylated glutamine analog, N-5-methylglutamine, during the synthesis of glutamine. GS inhibition leads to decreased levels of N-5-methylglutamine in the liver and circulation in mice. The levels of N-5-methylglutamine in urine correlate with tumor burden and GS expression in a liver cancer model.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Fuhui Chen, Sevim B. Gurler, David Novo, Cigdem Selli, Denis G. Alferez, Secil Eroglu, Kyriaki Pavlou, Jingwei Zhang, Andrew H. Sims, Neil E. Humphreys, Antony Adamson, Andrew Campbell, Owen J. Sansom, Cathy Tournier, Robert B. Clarke, Keith Brennan, Charles H. Streuli, Ahmet Ucar
Summary: Breast cancer stem cells (BCSC), responsible for treatment resistance, tumor recurrence, and metastasis, have been hindered by heterogeneity and lack of selective molecular targets. This study identifies RAC1B as a clinically relevant molecular target for BCSC-targeting therapies, highlighting its role in the maintenance of BCSC and their chemoresistance to doxorubicin.
Article
Oncology
Emma L. Wilkinson, Louise C. Brennan, Olivia J. Harrison, Zoe Crane-Smith, Philippe Gautier, Margaret A. Keighren, Peter Budd, Karthic Swaminathan, Laura M. Machesky, Sarah L. Allinson, Ian J. Jackson, Richard L. Mort
Summary: Genetic approaches are crucial for studying melanocytes and melanoma. Current methods for labeling melanocytes in mice have limitations, but researchers have successfully generated a targeted multicistronic allele using homologous recombination in mouse embryonic stem cells, allowing specific labeling and live imaging of melanocytes. This transgenic allele has been demonstrated to be useful in embryonic and adult tissues.
PIGMENT CELL & MELANOMA RESEARCH
(2023)
Article
Multidisciplinary Sciences
Clara Calvert, Jade Carruthers, Cheryl Denny, Jack Donaghy, Lisa E. M. Hopcroft, Leanne Hopkins, Anna Goulding, Laura Lindsay, Terry McLaughlin, Emily Moore, Bob Taylor, Maria Loane, Helen Dolk, Joan Morris, Bonnie Auyeung, Krishnan Bhaskaran, Cheryl L. Gibbons, Srinivasa Vittal Katikireddi, Maureen O'Leary, David McAllister, Ting Shi, Colin R. Simpson, Chris Robertson, Aziz Sheikh, Sarah J. Stock, Rachael Wood
Summary: This study using electronic health records from Scotland found no increased risk of congenital anomalies associated with COVID-19 vaccination or SARS-CoV-2 infection during early pregnancy.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Laura M. Machesky
Summary: Cells use actin-based protrusions to migrate, sample their environment, and take up liquids and particles. Lamellipodia and macropinocytic cups are involved in cell migration and uptake of surrounding substances. The regulation between these functions is not well understood.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Editorial Material
Cell Biology
Laura M. Machesky
Summary: Programmed cell death (PCD) helps cells to benefit the surviving organism. A recent study shows that cells can program their death by inducing extensive disulfide bonding of the actin cytoskeleton in response to an imbalance of cystine, a raw material for glutathione production.
NATURE CELL BIOLOGY
(2023)
Article
Medical Informatics
Lisa E. M. Hopcroft, Jon Massey, Helen J. Curtis, Brian Mackenna, Richard Croker, Andrew Brown, Thomas O'Dwyer, Orla Macdonald, David Evans, Peter Inglesby, Sebastian C. J. Bacon, Ben Goldacre, Alex J. Walker
Summary: This study developed and applied a hypothesis-free algorithm to identify unusual prescribing behavior in primary care data in England. The results were visualized using interactive dashboards, demonstrating the potential of data-driven approaches in identifying targets for improved healthcare delivery.
JMIR MEDICAL INFORMATICS
(2023)
Article
Oncology
Natasha Malik, Jodie Hay, Hassan N. B. Almuhanna, Karen M. Dunn, Jamie Lees, Jennifer Cassels, Jiatian Li, Rinako Nakagawa, Owen J. Sansom, Alison M. Michie
Summary: This study reveals the essential role of mTORC1 in the initiation/maintenance of leukemia in a CLL model and identifies the inactivation of eEF2 activity as a novel therapeutic target for blocking CLL progression.
Editorial Material
Biology
Laura Machesky
Article
Hematology
Charlie A. Coupland, Leigh Naylor-Adamson, Zoe Booth, Thomas W. Price, Helio M. Gil, George Firth, Michelle Avery, Yusra Ahmed, Graeme J. Stasiuk, Simon D. J. Calaminus
Summary: Approximately 17.3% of the global population suffers from zinc (Zn2+) deficiency, which leads to increased bleeding due to impaired hemostasis. Zinc ion (Zn2+) has the ability to modulate platelet signaling through the endothelial-derived prostacyclin I2 (PGI2) pathway, affecting thrombus formation and hemostasis.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Review
Oncology
Simon T. Barry, Dmitry I. Gabrilovich, Owen J. Sansom, Andrew D. Campbell, Jennifer P. Morton
Summary: Myeloid cells in the tumour microenvironment have a significant impact on tumour progression, making them a key target for clinical therapies. However, large-scale clinical trials targeting these cells have had limited success. Understanding the specific functions and roles of different myeloid cell subpopulations within the tumour microenvironment could improve the design of successful clinical trials for myeloid-targeting therapies.
NATURE REVIEWS CANCER
(2023)