Article
Multidisciplinary Sciences
Julia C. Reisenbauer, Ori Green, Allegra Franchino, Patrick Finkelstein, Bill Morandi
Summary: Reliable strategies for directly editing the core skeleton of pharmaceutical lead compounds are still scarce despite recent developments in the field. This study presents a method for skeletal editing of indoles through nitrogen atom insertion, demonstrating its utility in late-stage skeletal editing of several commercial drugs.
Article
Multidisciplinary Sciences
Aishwarya Swaminathan, Yung Hwang, Ashley Winward, Merav Socolovsky
Summary: This study developed a novel flow cytometric approach that allows for the isolation of pure subsets of BFU-e and CFU-e progenitors in mouse bone marrow, as well as the identification of other progenitor subsets.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Article
Physiology
Luis F. Delgadillo, Yu Shan Huang, Sami Leon, James Palis, Richard E. Waugh
Summary: The combined use of fluorescence labeling and micro-manipulation of red blood cells provides a powerful tool for understanding the mechanical behavior of cells. In this study, the development of the membrane-associated cytoskeleton (MAS) in embryonic erythroid cells was investigated using this approach. The results suggest that localization of cytoskeletal components to the cell membrane is not sufficient to produce a mature MAS, and additional processes are required to strengthen intraskeletal interactions.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Hematology
Michiko Ichii, Kenji Oritani, Jun Toda, Hideaki Saito, Henyun Shi, Hirohiko Shibayama, Daisuke Motooka, Yuichi Kitai, Ryuta Muromoto, Jun-ichi Kashiwakura, Kodai Saitoh, Daisuke Okuzaki, Tadashi Matsuda, Yuzuru Kanakura
Summary: STAP-2 is an adaptor protein that plays a role in the growth and development of B cells. It is not essential under normal conditions, but its absence enhances the recovery of B cells following transplantation. Further research on STAP-2 may provide insights into speeding up the recovery of humoral immunity in response to chemotherapy or transplantation.
Article
Multidisciplinary Sciences
Rashmi Bhardwaj, Lalit Kumar, Deepika Chhabra, N. K. Mehra, Atul Sharma, Sujata Mohanty, Vinod Kochupillai
Summary: This study explores the expansion of fetal liver hematopoietic stem cells in vitro, finding that a specific combination of 5 cytokines can optimally increase cell numbers with a cell viability greater than 90% throughout the 21-day culture period.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Koji Funato, Takaaki Abe, Ryo Kurita, Yoshihisa Watanabe, Yukio Nakamura, Shigeki Miyata, Yusuke Furukawa, Masahiro Satake
Summary: The production of red blood cells in vitro has been improved for basic or clinical research purposes. The study identified proteins showing reproducible differential expression during erythroid differentiation and found that most early-stage proteins were downregulated, while seven proteins showed upregulated expression in both bone marrow and cord blood cells. The roles of these proteins in erythropoiesis require further clarification, as they may contribute to erythroid differentiation.
Article
Medicine, Research & Experimental
Mathias Linnerbauer, Lena Losslein, Oliver Vandrey, Thanos Tsaktanis, Alexander Beer, Ulrike J. Naumann, Franziska Panier, Tobias Beyer, Lucy Nirschl, Joji B. Kuramatsu, Jurgen Winkler, Francisco J. Quintana, Veit Rothhammer
Summary: This study combines CNS single-cell transcriptome data and small-molecule screens to identify the potential therapeutic strategy of blocking ErbB signaling by afatinib in the treatment of acute and chronic stages of autoimmune CNS inflammation. The findings suggest that afatinib can mitigate proinflammatory astrocyte polarization, promote tissue-regenerative functions, reduce monocyte infiltration and axonal degeneration, and increase oligodendrocyte proliferation.
Article
Genetics & Heredity
Nazish N. Jeffery, Christina Davidson, Scott A. Peslak, Paul D. Kingsley, Yukio Nakamura, James Palis, Michael Bulger
Summary: This study reveals a potential role for the histone variant H2A.X in erythropoiesis, showing that its loss in erythroid cells leads to dysregulation in expression of erythroid-specific genes and nuclear condensation defect. Additionally, it demonstrates phosphorylation of H2A.X at both S139 and Y142 during late-stage erythropoiesis, and the knockout of BAZ1B/WSTF kinase results in loss of Y142 phosphorylation and a defect in nuclear condensation.
EPIGENETICS & CHROMATIN
(2021)
Article
Pharmacology & Pharmacy
Yasong Lu, Shuang Liang, Ying Hong, Naoyuki Tajima, Kashyap Patel, Hanbin Li, David R. Wada, Jon Greenberg, Adam Petrich, Hong Zebger-Gong, Dale Shuster, Pavan Vaddady
Summary: This article reports the application of a model-informed drug development approach during phase I to inform dose selection for the late-stage development of a TROP2-directed antibody-drug conjugate. The study found that the 6 mg/kg dose was more tolerable and more efficacious than the conventional maximum tolerated dose, demonstrating the utility of the model-informed drug development approach for dose optimization and selection.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Review
Hematology
Natascha Schippel, Shalini Sharma
Summary: Erythropoiesis, the development of erythrocytes, includes four phases and involves heterogeneity within the stem, progenitor, and erythroblast stages. Recent studies have revealed alternate paths for segregation of erythroid lineage potential. Flow cytometry remains the primary method for validation of novel immunophenotypes, despite the insights provided by single-cell RNA sequencing.
EXPERIMENTAL HEMATOLOGY
(2023)
Article
Hematology
Aditi Bapat, Natascha Schippel, Xiaojian Shi, Paniz Jasbi, Haiwei Gu, Mrinalini Kala, Aparna Sertil, Shalini Sharma
Summary: This study investigated the impact of low oxygen on myeloerythroid differentiation of human cord blood-derived hematopoietic stem cells, revealing that hypoxia promotes erythroid differentiation. The results demonstrate the extensive role of hypoxia at multiple steps during erythroid development.
EXPERIMENTAL HEMATOLOGY
(2021)
Article
Physiology
Daiki Watanabe, Masanobu Wada
Summary: The study examined the effects of reduced glutathione (GSH) on skeletal muscle fatigue. GSH levels were decreased by treating male Wistar rats with buthionine sulfoximine (BSO) for 5 days. Muscle force and physiological functions were measured before and after fatiguing stimulation (FS) and rest. The results showed that GSH depression altered the cellular mechanism of muscle fatigue and delayed force recovery due to prolonged calcium leakage from the sarcoplasmic reticulum (SR) in the late stage of recovery.
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY, INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
(2023)
Article
Astronomy & Astrophysics
Motoharu Nowada, Yukinaga Miyashita, Noora Partamies, Alexander William Degeling, Quan-Qi Shi
Summary: The Polar spacecraft's ultraviolet imager (UVI) and a ground-based all-sky camera detected an auroral vortex structure on 10 January 1997. The auroral spiral appeared in the poleward region of the main auroral oval and was formed during the late substorm recovery phase. Ground magnetic stations around Svalbard island observed significant variations in the north-south and east-west components of the geomagnetic field during the spiral period. Results suggest that the source region of the auroral spiral covered a broad region in the magnetotail, indicating the continued activity of the magnetotail even during stable geomagnetic conditions.
JOURNAL OF GEOPHYSICAL RESEARCH-SPACE PHYSICS
(2023)
Article
Cell & Tissue Engineering
Hongtao Wang, Jian He, Changlu Xu, Xiaoyuan Chen, Hua Yang, Shujuan Shi, Cuicui Liu, Yang Zeng, Dan Wu, Zhijie Bai, Mengge Wang, Yuqi Wen, Pei Su, Meijuan Xia, Baiming Huang, Chunyu Ma, Lihong Bian, Yu Lan, Tao Cheng, Lihong Shi, Bing Liu, Jiaxi Zhou
Summary: Through single-cell RNA sequencing, it was found that early human megakaryopoiesis in embryonic and fetal stages exhibits cellular heterogeneity, with different MK subpopulations expressing distinct gene patterns that may reflect early functional specialization. Additionally, a subpopulation of MKs expressing genes associated with immune responses was identified in vivo, and these cells could also be derived from human embryonic stem cells.
Article
Immunology
Yan Xu, Zheng Xiang, Mohammed Alnaggar, Leonce Kouakanou, Jiawei Li, Junyi He, Jiashuang Yang, Yi Hu, Yan Chen, Li Lin, Jianlei Hao, Jingxia Li, Jibing Chen, Man Li, Qingling Wu, Christian Peters, Qinghua Zhou, Jianshuang Li, Yingqing Liang, Xiaohua Wang, Baohui Han, Meili Ma, Dieter Kabelitz, Kecheng Xu, Wenwei Tu, Yangzhe Wu, Zhinan Yin
Summary: The study focused on utilizing allogeneic V gamma 9V delta 2 T cells for tumor immunotherapy, developing a novel formula for expanding gamma delta T cells from healthy donors, and conducting clinical trials to prove the safety and efficacy of allogeneic V gamma 9V delta 2 T cells, showing promising results in late-stage cancer patients.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Hematology
Peng Huang, Scott A. Peslak, Xianjiang Lan, Eugene Khandros, Jennifer A. Yano, Malini Sharma, Cheryl A. Keller, Belinda Giardine, Kunhua Qin, Osheiza Abdulmalik, Ross C. Hardison, Junwei Shi, Gerd A. Blobel
Article
Hematology
Eugene Khandros, Peng Huang, Scott A. Peslak, Malini Sharma, Osheiza Abdulmalik, Belinda M. Giardine, Zhe Zhang, Cheryl A. Keller, Ross C. Hardison, Gerd A. Blobel
Article
Medicine, Research & Experimental
Daphne N. Pariser, Zachary T. Hilt, Sara K. Ture, Sara K. Blick-Nitko, Mark R. Looney, Simon J. Cleary, Estheany Roman-Pagan, Jerry Saunders, Steve N. Georas, Janelle Veazey, Ferralita Madere, Laura Tesoro Santos, Allison Arne, Nguyen P. T. Huynh, Alison C. Livada, Selena M. Guerrero-Martin, Claire Lyons, Kelly A. Metcalf-Pate, Kathleen E. McGrath, James Palis, Craig N. Morrell
Summary: Platelets, previously known as cellular mediators of thrombosis, are also immune cells that interact with immune cells, impacting their activation and differentiation. Lung megakaryocytes (Mk(L)) have gene expression patterns similar to antigen-presenting cells, and have key immune regulatory roles influenced by the tissue environment. This indicates the plasticity of the immune phenotype of Mk(L) and their ability to induce T cell activation.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Biology
J. Saunders, L. M. Niswander, K. E. McGrath, A. Koniski, S. C. Catherman, S. K. Ture, M. Medhora, P. D. Kingsley, L. M. Calvi, J. P. Williams, C. N. Morrell, J. Palis
Summary: The combined therapy of 16,16-dimethyl prostaglandin E-2 and lisinopril was found to effectively mitigate thrombocytopenia in hematopoietic-acute radiation syndrome and improve survival. Experiments on murine models demonstrated that this combination therapy has a positive impact on the recovery of the megakaryocyte lineage and its niche.
RADIATION RESEARCH
(2021)
Article
Genetics & Heredity
Nazish N. Jeffery, Christina Davidson, Scott A. Peslak, Paul D. Kingsley, Yukio Nakamura, James Palis, Michael Bulger
Summary: This study reveals a potential role for the histone variant H2A.X in erythropoiesis, showing that its loss in erythroid cells leads to dysregulation in expression of erythroid-specific genes and nuclear condensation defect. Additionally, it demonstrates phosphorylation of H2A.X at both S139 and Y142 during late-stage erythropoiesis, and the knockout of BAZ1B/WSTF kinase results in loss of Y142 phosphorylation and a defect in nuclear condensation.
EPIGENETICS & CHROMATIN
(2021)
Article
Cell Biology
Yi Zhang, Kathleen E. McGrath, Edward Ayoub, Paul D. Kingsley, Hongbo Yu, Kate Fegan, Kelly A. McGlynn, Sarah Rudzinskas, James Palis, Archibald S. Perkins
Summary: The research revealed that HSC-derived erythroid, myeloid, and lymphoid progeny significantly expand in the liver and blood stream between E14.5 and E16.5, highlighting the importance of HSC contribution.
Article
Immunology
Michael H. Atkins, Rebecca Scarfo, Kathleen E. McGrath, Donghe Yang, James Palis, Andrea Ditadi, Gordon M. Keller
Summary: Specific populations of immune cells in the adult originates from the embryonic yolk sac independently of hematopoietic stem cells. Research using human pluripotent stem cell model has successfully mapped human yolk sac hematopoiesis to understand developmentally restricted progenitors. The study suggests that yolk sac-derived immune cell progeny seed developing tissues and function into adult life, with a potential common progenitor for EMP and lymphoid lineages identified through clonal analyses.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Physiology
Luis F. Delgadillo, Yu Shan Huang, Sami Leon, James Palis, Richard E. Waugh
Summary: The combined use of fluorescence labeling and micro-manipulation of red blood cells provides a powerful tool for understanding the mechanical behavior of cells. In this study, the development of the membrane-associated cytoskeleton (MAS) in embryonic erythroid cells was investigated using this approach. The results suggest that localization of cytoskeletal components to the cell membrane is not sufficient to produce a mature MAS, and additional processes are required to strengthen intraskeletal interactions.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Hematology
Travis Nemkov, Paul D. Kingsley, Monika Dzieciatkowska, Jeffrey Malik, Kathleen E. McGrath, Kirk C. Hansen, Angelo D'Alessandro, James Palis
Summary: This study analyzed the proteome, metabolome, and lipidome of primitive erythroblasts at different stages of maturation. The results revealed changes in organelle-specific protein components, metabolic pathways, redox homeostasis, and cholesterol synthesis. These findings provide insights into the metabolic adaptations and functional transitions during the maturation of primitive erythroid precursors.
Article
Genetics & Heredity
Kunhua Qin, Peng Huang, Ruopeng Feng, Cheryl A. Keller, Scott A. Peslak, Eugene Khandros, Megan S. Saari, Xianjiang Lan, Thiyagaraj Mayuranathan, Phillip A. Doerfler, Osheiza Abdulmalik, Belinda Giardine, Stella T. Chou, Junwei Shi, Ross C. Hardison, Mitchell J. Weiss, Gerd A. Blobel
Summary: NFIA and NFIX, members of the NFI transcription factor family, repress the expression of fetal-type beta-globin-like genes HBG1 and HBG2 in adult erythroid cells. This repression is achieved through the stimulation of BCL11A, a known silencer of HBG1/2 genes, and direct repression of HBG1/2 genes by NFIA and NFIX.
Article
Genetics & Heredity
Peng Huang, Scott A. Peslak, Ren Ren, Eugene Khandros, Kunhua Qin, Cheryl A. Keller, Belinda Giardine, Henry W. Bell, Xianjiang Lan, Malini Sharma, John R. Horton, Osheiza Abdulmalik, Stella T. Chou, Junwei Shi, Merlin Crossley, Ross C. Hardison, Xiaodong Cheng, Gerd A. Blobel
Summary: HIC2 regulates the fetal-to-adult hemoglobin switch by inhibiting the transcription of the BCL11A gene through reducing chromatin accessibility and displacing the GATA1 transcription factor. It plays a crucial role in the developmental control of BCL11A and is important for hemoglobin switching.
Letter
Hematology
Scott A. Peslak, Alexis Brimm Akins, Anessa M. Foxwell, Marie Iannelli, Carolyn Grande, Delisha Breen, J. Eric Russell, Tanya J. Uritsky, Farzana A. Sayani
Article
Medicine, Research & Experimental
Scott A. Peslak, Selami Demirci, Vemika Chandra, Byoung Ryu, Saurabh K. Bhardwaj, Jing Jiang, Jeremy W. Rupon, Robert E. Throm, Naoya Uchida, Alexis Leonard, Khaled Essawi, Aylin C. Bonifacino, Allen E. Krouse, Nathaniel S. Linde, Robert E. Donahue, Francesca Ferrara, Matthew Wielgosz, Osheiza Abdulmalik, Nicole Hamagami, Paula Germino-Watnick, Anh Le, Rebecca Chu, Malikiya Hinds, Mitchell J. Weiss, Wei Tong, John F. Tisdale, Gerd A. Blobel
Summary: This study demonstrates that forced enhancer rewiring can alter gene expression and presents a potential strategy for therapeutic purposes. By transducing hematopoietic stem and progenitor cells (HSPCs) with lentiviral vectors expressing a synthetic transcription factor (ZF-Ldb1) and forcing contact between the enhancer and the target gene, elevated expression of the target gene was achieved in adult-type erythroid cells. This proof of concept was demonstrated in both mice and rhesus macaque models.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Correction
Genetics & Heredity
Peng Huang, Scott A. Peslak, Ren Ren, Eugene Khandros, Kunhua Qin, Cheryl A. Keller, Belinda Giardine, Henry W. Bell, Xianjiang Lan, Malini Sharma, John R. Horton, Osheiza Abdulmalik, Stella T. T. Chou, Junwei Shi, Merlin Crossley, Ross C. Hardison, Xiaodong Cheng, Gerd A. Blobel
Article
Oncology
Vera Adema, Feiyang Ma, Rashmi Kanagal-Shamanna, Natthakan Thongon, Guillermo Montalban-Bravo, Hui Yang, Scott A. Peslak, Feng Wang, Pamela Acha, Francesc Sole, Pamela Lockyer, Margherita Cassari, Jaroslaw P. Maciejewski, Valeria Visconte, Irene Ganan-Gomez, Yuanbin Song, Carlos Bueso-Ramos, Matteo Pellegrini, Tuyet M. Tan, Rafael Bejar, Jennifer S. Carew, Stephanie Halene, Valeria Santini, Gheath Al-Atrash, Karen Clise-Dwyer, Guillermo Garcia-Manero, Gerd A. Blobel, Simona Colla
Summary: SF3B1 mutations in MDS-RS activate the EIF2AK1 pathway, which leads to abnormal erythroid differentiation. Targeting this pathway may rescue red blood cell production.
BLOOD CANCER DISCOVERY
(2022)