Article
Biology
Elitsa Stoyanova, Michael Riad, Anjana Rao, Nathaniel Heintz
Summary: At birth, the mammalian brain contains billions of neurons, which develop into networks and learn adult brain tasks through chemical marks such as methylation and hydroxymethylation. Accumulation of 5hmC, possibly essential for neuronal maturation, highlights the role of Tet proteins in preparing and removing DNA marks. Problematic control of 5hmC levels could potentially contribute to brain disorders, while future studies may provide insights into cancerous cell development due to loss of 5hmC.
Article
Biochemistry & Molecular Biology
Chirada Dusadeemeelap, Thira Rojasawasthien, Takuma Matsubara, Shoichiro Kokabu, William N. Addison
Summary: This study investigates the role of TET-mediated DNA hydroxymethylation in bone formation using a novel selective TET enzyme inhibitor, BC339. The results show that inhibiting TET with BC339 suppresses osteoblast differentiation and functions through increasing the methylation level of the Sp7 promoter.
Article
Immunology
Lifei Hou, Koichi Yuki
Summary: CD11a plays a critical role in leukocyte arrest and immunological synapse formation, but its role in the bone marrow is not well studied. This research showed that CD11a is expressed on all subsets of hematopoietic stem and progenitor cells (HPSCs). CD11a deficiency enhances HSPCs activity under LPS stimulation, possibly by upregulating the production of IL-27 to promote cell proliferation.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Multidisciplinary Sciences
Mitinori Saitou, Katsuhiko Hayashi
Summary: Considerable advances have been made in in vitro gametogenesis, allowing the induction of functional germ cells from pluripotent stem cells for research on mammalian germ cell development mechanisms and exploration of infertility treatments.
Article
Cell Biology
Naoko Irie, Sun-Min Lee, Valentina Lorenzi, Haiqi Xu, Jinfeng Chen, Masato Inoue, Toshihiro Kobayashi, Carmen Sancho-Serra, Elena Drousioti, Sabine Dietmann, Roser Vento-Tormo, Chun-Xiao Song, M. Azim Surani
Summary: The commitment of germline during early human development is crucial for the subsequent gametogenesis. A study on PGC-like cells derived from human embryonic stem cells reveals that the induction of DMRT1 and SOX17 promotes epigenetic resetting and the expression of DNA methylation-sensitive genes, indicating the initiation of the germline commitment programme.
NATURE CELL BIOLOGY
(2023)
Article
Developmental Biology
Shizheng Zhao, Ao Zhang, Hao Zhu, Zilong Wen
Summary: The study reports the identification and characterization of a new member of the ETS transcription factors, Spi2, in ray-finned fish. It shows that Spi2 is crucial for hematopoietic stem and progenitor cell development and myeloid lineage differentiation. A reporter line is created to track these cells from early development to adulthood.
Article
Biochemistry & Molecular Biology
You Jung Hwang, Dong-Yeop Shin, Min-Jung Kim, Hyosun Jang, Soyeon Kim, Hyunwon Yang, Won Il Jang, Sunhoo Park, Sehwan Shim, Seung Bum Lee
Summary: This study found that SR1 could alleviate radiation-induced hematopoietic injury. It increased the survival rate and promoted the recovery of peripheral blood cell counts in irradiated mice. In vitro experiments also showed that SR1 increased the population of human hematopoietic stem/progenitor cells, reduced radiation-induced DNA damage and apoptosis. These results suggest that SR1 may be a potential radiomitigator for hematopoietic injury.
Article
Cell & Tissue Engineering
Kenji Kitajima, Minako Shingai, Hikaru Ando, Mako Hamasaki, Takahiko Hara
Summary: Researchers developed a novel method for hematopoietic differentiation of human-induced pluripotent stem cells to address the issue of low production of CD38(+) hematopoietic progenitor cells. They found that the lack of FLT3 expression was responsible for this problem and solved it by adding interferon-gamma.
Article
Multidisciplinary Sciences
Leal Oburoglu, Els Mansell, Niels-Bjarne Woods
Summary: Glutamine metabolism plays an essential role in regulating the emergence and specification of hematopoietic cells during endothelial to hematopoietic transition (EHT), with different hematopoietic lineages requiring distinct derivatives of glutamine.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Irene Mariam Roy, P. V. Anu, Samantha Zaunz, Srinu Reddi, Aravind M. Giri, Rithika Saroj Sankar, Sarah Schouteden, Joerg Huelsken, Catherine M. Verfaillie, Satish Khurana
Summary: Interaction with microenvironmental factors is crucial for the regulation of hematopoietic stem cell function. In this study, it was found that integrin signaling regulates the expression of SDF-1 alpha through transcriptional regulation. Inhibition of SRC gene or pharmacological inhibition resulted in increased expression of the chemokine SDF-1 alpha. Systemic inhibition of SRC led to increased SDF-1 alpha levels in BM plasma, which improved the homing efficiency of transplanted HSCs and enhanced hematopoietic function.
Article
Cell & Tissue Engineering
Zhengqi Wang, Grace Emmel, Hong Seo Lim, Wandi Zhu, Astrid Kosters, Eliver E. B. Ghosn, Peng Qiu, Kevin D. Bunting
Summary: This study reveals the important role of STAT5ab gene in both hematopoietic and stromal cells, and the deletion of STAT5ab using specific Cre promoters leads to a reduction in multipotent hematopoietic progenitors. Furthermore, STAT5ab is involved in the secretion of niche factors in mesenchymal stem cells and the differentiation priming of hematopoietic stem cells.
Review
Developmental Biology
Aidan H. Terhune, Jeyoon Bok, Shiyu Sun, Jianping Fu
Summary: The development of a zygote into an embryo is a miraculous process in nature, but scientists have struggled to understand the mechanisms in human embryos due to ethical and practical limitations. However, pluripotent stem cells have the ability to mimic specific embryonic events, allowing the creation of in vitro models that recapitulate different stages of early embryo development.
Article
Multidisciplinary Sciences
Huiqin Cao, Wei Wei, Ruirong Xu, Xing Cui
Summary: The study demonstrates that Rg1 can improve hematopoietic function in AA model mice by inhibiting Bax translocation, promoting mitochondrial function recovery.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Li-Sheng Zhang, Qing-Ping Xiong, Sonia Pena Perez, Chang Liu, Jiangbo Wei, Cassy Le, Linda Zhang, Bryan T. Harada, Qing Dai, Xinran Feng, Ziyang Hao, Yuru Wang, Xueyang Dong, Lulu Hu, En-Duo Wang, Tao Pan, Arne Klungland, Ru-Juan Liu, Chuan He
Summary: ALKBH7 is identified as an RNA demethylase that controls nascent mitochondrial RNA processing and mitochondrial activity, with depletion leading to increased processing of polycistronic mitochondrial RNA, reduced levels of mitochondria-encoded tRNA and protein translation, as well as decreased mitochondrial activity.
NATURE CELL BIOLOGY
(2021)
Review
Cell Biology
Bonsang Koo, Ki-Heon Lee, Guo-li Ming, Ki-Jun Yoon, Hongjun Song
Summary: Radial glial cells (RGCs) are primary neural stem cells in the mammalian cortex, and they give rise to different types of neurons and glial cells with precise spatio-temporal development. Epigenetic and epitranscriptomic regulatory mechanisms, including DNA methylation, histone modifications, and chromatin architecture, play crucial roles in controlling the temporal competence of RGCs during mammalian corticogenesis. Various developmental elements, such as biochemical reaction speed, local environmental changes, and subcellular organelle remodeling, also dynamically regulate the temporal competence of RGCs. Additionally, the underlying mechanisms regulating interspecies developmental tempo contribute to human-specific features of brain development.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Stephanie Chrysanthou, Qin Tang, Joun Lee, Samuel J. Taylor, Yilin Zhao, Ulrich Steidl, Deyou Zheng, Meelad M. Dawlaty
Summary: Research has found that the critical functions of Tet1 in embryonic stem cells and early development are mediated through its non-catalytic roles in regulating H3K27 modifications, which are more important than its catalytic functions in DNA demethylation.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Claudia Morganti, Kyoko Ito, Chie Yanase, Amit Verma, Julie Teruya-Feldstein, Keisuke Ito
Summary: This study identifies the role of NPM1 in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). NPM1 deficiency leads to premature aging of hematopoietic stem cells (HSCs), resulting in inflammation and the development of MDS-like phenotype. Additionally, the study highlights the role of p53 in the progression of MDS to leukemia.
Article
Clinical Neurology
Maider Astorkia, Herbert M. Lachman, Deyou Zheng
Summary: In this study, by analyzing single-cell RNA-seq data, we identified disrupted intercellular signaling pathways in the brains of individuals with autism spectrum disorder. These disruptions involve both neurons and glia cells, with excitatory and inhibitor neurons showing increased strength in intercellular signaling, such as NRXN and CNTN signaling. Despite moderate changes, the genes involved in these affected signaling pathways are enriched for critical cellular functions related to axon guidance, synapse organization, and neuron migration. Furthermore, these genes are highly connected to and enriched for genes previously associated with autism risks.
JOURNAL OF NEURODEVELOPMENTAL DISORDERS
(2022)
Article
Multidisciplinary Sciences
Peter John, Marc C. Pulanco, Phillip M. Galbo, Yao Wei, Kim C. Ohaegbulam, Deyou Zheng, Xingxing Zang
Summary: B7x, an immune checkpoint molecule, promotes the conversion of CD4+ T cells into regulatory T cells within the tumor microenvironment. It induces transcriptomic changes in regulatory T cells, altering their phenotype to an activated and suppressive state. B7x-mediated regulation reduces the efficacy of anti-CTLA-4 treatment, but combination therapy with anti-B7x and anti-CTLA-4 overcomes this resistance and shows synergistic therapeutic efficacy.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Elodie Picarda, Phillip M. Galbo, Haihong Zong, Meenu Rohini Rajan, Ville Wallenius, Deyou Zheng, Emma Borgeson, Rajat Singh, Jeffrey Pessin, Xingxing Zang
Summary: The immune checkpoint B7-H3 has been studied in the tumor microenvironment and immunotherapy, but its potential role in metabolism remains largely unknown. This study reveals that B7-H3 is highly expressed in adipose tissue, particularly in adipocyte progenitor cells, and it regulates the glycolytic and mitochondrial activity of these cells. Loss of B7-H3 leads to impaired oxidative metabolism and increased lipid accumulation in derived adipocytes. Knockout of B7-H3 in mice results in spontaneous obesity, metabolic dysfunction, and adipose tissue inflammation.
Article
Biochemical Research Methods
Vinod Kumar Singh, Rohan Misra, Steven C. Almo, Ulrich G. Steidl, Hannes E. Bulow, Deyou Zheng
Summary: A new method has been proposed to search for motifs in biopolymer sequences that exist in non-single-letter contexts. The modified sequence elements are converted to representative single-letter codes and a modified Gibbs-sampling algorithm is used to define the position specific scoring matrix representing the motifs.
Review
Cell & Tissue Engineering
Lidiane S. Torres, Noboru Asada, Mitchell J. Weiss, Andreas Trumpp, Toshio Suda, David T. Scadden, Keisuke Ito
Summary: This article reviews the two research topics, sickle cell disease and the hematopoietic stem cell niche, that formed the basis of Dr. Paul S. Frenette's outstanding career. The first part discusses important discoveries in sickle cell disease pathophysiology and recent advances in its treatment. The second part focuses on the complex microenvironment within the bone marrow that controls hematopoietic stem cell function and homeostasis, highlighting key aspects of Dr. Frenette's research and his significant scientific contributions in both fields.
Article
Immunology
Richard T. Piszczatowski, Emily Schwenger, Sriram Sundaravel, Catarina M. Stein, Yang Liu, Pamela Stanley, Amit Verma, Deyou Zheng, Ronald D. Seidel, Steven C. Almo, Robert A. Townley, Hannes E. Buelow, Ulrich Steidl
Summary: Heparan sulfate (HS) glycotyping plays an important role in hematopoietic lineage differentiation and can be used to identify and stratify different cell types. By utilizing a panel of anti-HS single-chain variable fragment antibodies (scFvs), functionally distinct glycotypes within heterogeneous cell populations can be identified and further purified.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Athanasia Stathopoulou, Ping Wang, Charlotte Thellier, Robert G. Kelly, Deyou Zheng, Peter J. Scambler
Summary: This study investigates the role of CHD7 protein in cardiac development. The results show that CHD7 is necessary for the correct expression of genes involved in cardiac development, particularly in the second heart field. The study also reveals the interaction between CHD7 and ISL1, and their involvement in the regulation of cardiac enhancers during heart morphogenesis.
CARDIOVASCULAR RESEARCH
(2023)
Article
Hematology
Julio C. Flores, Kyoko Ito, Cheng-Yen Huang, Qin Tang, Chie Yanase, Keisuke Ito, Meelad M. Dawlaty
Summary: TET2 is a member of the Ten-eleven translocation (Tet) family and plays a role in regulating gene expression through DNA demethylation and chromatin modification. It is highly expressed in the hematopoietic lineage and its mutations are associated with hematologic malignancies. This study reveals the different impacts of TET2 catalytic and noncatalytic functions on myeloid and lymphoid lineages during hematopoiesis.
EXPERIMENTAL HEMATOLOGY
(2023)
Article
Multidisciplinary Sciences
Christopher De Bono, Yang Liu, Alexander Ferrena, Aneesa Valentine, Deyou Zheng, Bernice E. Morrow
Summary: Disruption of cardiac neural crest cells (CNCCs) leads to congenital heart disease. The cell fate dynamics of CNCCs differentiating into vascular smooth muscle cells are not well understood. This study used single-cell RNA-sequencing to analyze the differentiation process of CNCCs in control mouse embryos and in embryos with inactivated Tbx1. The results reveal the dynamic transitions of CNCCs and the role of Tbx1 in this process, as well as the consequences of Tbx2 and Tbx3 inactivation on aortic arch branching and smooth muscle differentiation.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Keisuke Ito, Teresa V. Bowman