INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Jiacheng Wang,Yuhang Zhang,Yingbin Xu,Hongyu Jin,Can Yang,Hongxing Liu,Yongbo Bao
The blood clam ( Anadara granosa ) exhibits innovative red blood compared to other molluscs, with erythrocytes constituting 79 % to 89 % of the total hemocyte count. Previously, we identified that GATA-binding protein 1 (designated as Ag GATA1) was significantly up-regulated in the transcriptomes of blood clam populations with high hemocyte counts. However, the function of Ag GATA1 in erythropoiesis remains unknown. In this study, we conducted GATA1 knockdown experiments in A. granosa , which resulted in a significant reduction of both erythrocytes and other cells during the S phase, as well as significantly decreased proliferative activity in the gill tissue. The cell proliferation assay demonstrated that overexpression of Ag GATA1 increased the DNA replication activity of K562 cells. Additionally, o-dianisidine staining revealed defects in erythropoiesis within the gill tissue following Ag GATA1 knockdown, while protein analyses confirmed a significant reduction in Ag GATA1 expression. Furthermore, decreased cytoskeletal fluorescence and morphological changes in erythrocytes suggest that Ag GATA1 influenced cytoskeletal protein expression, leading to changes in erythrocyte morphology. This study provides new insights into the role of Ag GATA1 in hemocyte formation and highlights its significance in understanding erythropoiesis within invertebrate developmental tissues.
研究领域:
分子生物学
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发育生物学
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DOI
PubMed
高影响因子
Advanced Science
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2026
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IF 14.1
Wenxin Huang,Yi Sun,Yanxin Wang,Haijun Yan,Xiaoping Yue,Weidong Wu,Xueyu Chen,Jinfang Zhang,Yanbing Lin,Qiong Lei,Nan Ji,Shuaishuai Xing,Liqin Zeng,Qingzheng Kang,Depeng Zhao,Geng Guo,Huidong Zhang
The pathogenesis of unexplained miscarriage (UM) is largely unclear. Environmental Zn pollution is widely present in various environments and inevitably ingested by pregnant women, which has shown reproductive toxicity. Disulfidptosis is a newly identified programmed cell death caused by excessive disulfide stress. Notably, the association, causation, and underlying mechanisms among Zn exposure, disulfidptosis, and unexplained miscarriage are completely unknown. In this study, based on two UM case-control groups, four ZnCl 2 -exposed mouse models, and a ZnCl 2 -exposed trophoblast Swan 71 cell model, we obtain a consistent conclusion that excessive Zn exposure causes disulfidptosis and thus induces miscarriage by up-regulating the GATA1/METTL1/SLC7A11 axis. In the mechanism, Zn exposure up-regulates GATA1 expression levels, which promotes GATA1-mediated METTL1 and SLC7A11 transcription. Meanwhile, Zn exposure also promotes METTL1-mediated m7G modification on SLC7A11 mRNA and thus increases SLC7A11 mRNA stability. Ultimately, Zn exposure up-regulates SLC7A11 expression levels at both transcription and post-transcription levels and thus causes disulfidptosis. Knockdown of murine Slc7a11, Gata1, or Mettl1, or supplement with NADPH suppresses mouse placental disulfidptosis and alleviates mouse miscarriage. This study not only discovers pathogenesis and biological mechanisms of Zn exposure-induced unexplained miscarriage but also provides potential targets, uncovering new health risk effects of Zn exposure in the environment-health field.
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DOI
PubMed
高影响因子
Scientific Reports
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2026
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IF 4.9
Wang Ying,Zhang Qi,Liu Jiahui,Kuang Hongying,Feng Xiaoling
Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder among women of childbearing age and the leading cause of anovulatory infertility worldwide, with the death of granulosa cells implicated in its pathogenesis. However, the mechanisms underlying granulosa cell death remain unclear. Limited research has explored the association between GATA binding factor 1 (GATA1) and adverse pregnancy outcomes, yet its role in PCOS is still elusive. This study established an in vivo PCOS model via dehydroepiandrosterone administration in mice and used ovarian-like KGN cells to explore granulosa cell function. Results showed elevated ovarian GATA1 expression in PCOS mice. Functionally, GATA1 overexpression in KGN cells increased lipid reactive oxygen species, malondialdehyde, and iron, while reducing glutathione. Notably, all these effects of GATA1 were mitigated by a ferroptosis inhibitor Ferrostatin-1. Furthermore, GATA1 knockdown alleviated lipid peroxidation and iron overload in KGN cells induced by a ferroptosis inducer Erastin. Mechanistically, GATA1 directly bound the transferrin receptor (TFRC) promoter to enhance its transcription. Additionally, TFRC overexpression counteracted GATA1 knockdown’s protective effects against Erastin-induced ferroptosis. Collectively, GATA1 promotes granulosa cell ferroptosis via TFRC transcriptional activation, contributing to PCOS pathogenesis. GATA1 regulatory pathways may serve as potential therapeutic targets for PCOS.
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高影响因子
Cell Death Discovery
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2026
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IF 10.4
Chen Yu,Wen Yuetao,Xu Diru,Hao Lei,Liu Qinglin,Kuang Jia,Zhao Wang,Yang Zhao
Depression is associated with complex hippocampal pathology, including disrupted signaling and neuronal damage. In this study, we developed a novel targeted nanoplatform using nucleic acid aptamer-modified astrocyte-derived extracellular vesicles loaded with geniposide (Apt-EVs@GP) to investigate its therapeutic mechanism, with a focus on the GATA binding protein 1 (GATA1)/adrenergic receptor beta 2 (ADRB2) axis in a chronic unpredictable mild stress (CUMS) mouse model. Apt-EVs@GP exhibited excellent biocompatibility and targeted accumulation in the hippocampus. Apt-EVs@GP treatment significantly ameliorated depression-like behaviors, as evidenced by enhanced locomotor activity and reduced immobility in standard behavioral assays. Transcriptomic analysis combined with molecular validation identified a key regulatory mechanism: Apt-EVs@GP suppressed stress-induced upregulation of GATA1, thereby relieving its transcriptional repression of ADRB2. This regulatory interaction was confirmed by chromatin immunoprecipitation and dual-luciferase reporter assays. Restoration of ADRB2 expression led to robust activation of the downstream cAMP/PKA/CREB signaling pathway. Functionally, reprogramming of the GATA1/ADRB2/cAMP axis conferred comprehensive hippocampal protection, including attenuation of neuroinflammation, suppression of neuronal apoptosis, and restoration of synaptic integrity. Our findings demonstrate that Apt-EVs@GP alleviates depression by targeting a novel GATA1/ADRB2 mechanism, highlighting its potential as a promising therapeutic strategy against depression-related hippocampal pathology. The alternative text for this image may have been generated using AI.
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PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
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2019
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IF 1.984
Liwen Han,Haotian Kong,Fasheng Liu,Xiaobin Li,Shanshan Zhang,Xuanming Zhang,Yong Wu,Hua Yang,Aiping Zhang,Kechun Liu
The aim of the study is to explore the protective effect of new gelatin (NG, Xin’ejiao in China) on hematopoietic injury caused by chemotherapy. Zebrafish, at 48 hours post fertilization (hpf), was treated with different chemotherapeutic drugs to establish the zebrafish hematopoietic damage model with reduced thrombocytes and erythrocytes. The protecting effects of NG on the thrombocytes and erythrocytes were observed, respectively, on zebrafish models. Then, the RT-PCR method was used to detect the change of mRNA level of the hematopoiesis-related cytokines scl1, c-myb, pu.1, GATA1, and runx1 genes. The results showed that 50 μg·mL−1 and 100 μg·mL−1 NG rescued and increased the thrombocytes numbers induced by vinorelbine (NVB) and chloramphenicol (CHL) and the erythrocytes numbers induced by methotrexate (MTX), doxorubicin (ADM), and mechlorethamine hydrochloride (MH) in zebrafish models. Meanwhile, the mRNA expression of scl1, c-myb, and GATA1 genes in the NG treatment group was raised compared with the MTX treatment group. Also, the mRNA expression of pu.1 and Runx1 in the NG treatment group was reduced compared with the MTX treatment group. In consequence, traditional Chinese medicine NG showed a certain degree protective effect on hematopoiesis injury induced by chemotherapy in this study, which may depend on the promotion of erythrocytes proliferation and the regulation of the hematopoietic genes level.
研究领域:
药理学
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血液学
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分子生物学
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斑马鱼研究
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PubMed
高影响因子
STAR Protocols
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2022
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IF 0
Yanyan Ding,Feng Liu
Summary Understanding chromatin dynamics in red blood cells (RBCs) is critical for exploring the differentiation process and homeostasis maintenance during erythropoiesis. Here, we describe a protocol for isolation of zebrafish erythrocytes labelled with gata1 :dsRed by fluorescence-activated cell sorting. We detail steps for ATAC-seq library construction from the isolated RBCs and describe how to analyze the quality of the library. The library can then be used to assay genome-wide chromatin accessibility in these RBCs. For complete details on the use and execution of this protocol, please refer to Ding et al. (2021). 1
研究领域:
基因组学
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分子生物学
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血液学
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DOI
PubMed
iScience
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2023
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IF 5.8
Yao Li,Zi-Yu Liang,Hai-Lin Wang
Summary Red blood cells supply the oxygen required for all human cells and are in demand for emerging blood-loss therapy. Here we identified N6-methyl-2′-deoxyadenosine (6mdA) as an agonist that promotes the hyperproliferation of burst-forming unit erythroid (BFU-E) progenitor cells. In addition, 6mdA represses the apoptosis of erythroid progenitor cells (EPCs). Combined use of with SCF and EPO enabled cultures of isolated BFU-E to be expanded up to 5,000-fold. Transcriptome analysis showed that 6mdA upregulates the expression of the EPC-associated factors c-Kit, Myb, and Gata2 and downregulates that of the erythroid maturation-related transcription factors Gata1, Spi1, and Klf1. Mechanistic studies suggested that 6mdA enhances and prolongs the activation of erythropoiesis-associated master gene c-Kit and its downstream signaling, leading to expansion and accumulation of EPCs. Collectively, we demonstrate that 6mdA can efficiently stimulate the EPC hyperproliferation and provide a new regenerative medicine recipe to improve ex vivo generation of red blood cells.
研究领域:
血液学
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分子生物学
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再生医学
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细胞生物学
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DOI
PubMed
高影响因子
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