2020 Vol. 11, No. 9

SARS-CoV-2 infection resulted in mucins hypersecretionin lung, along with impaired mucociliary clearance viaciliary dysfunction. Mucin hypersecretion and altered mucinmacromolecular organization form a dysfunctional mucus gel.As a consequence, mucus accumulated in airways obstructsthe respiratory tract lumen and limits airflow, which leading tothe ARDS and human death.
Pioneer of burn medicine in China: Professor Li Ao and “Li Ao spirit”
Yaling Liao, Quaming Zou, Jiang Gu
2020, 11(9): 621-623. doi: 10.1007/s13238-020-00703-z
The expanded development and application of CRISPR system for sensitive nucleotide detection
Fengjing Jia, Xuewen Li, Chao Zhang, Xueming Tang
2020, 11(9): 624-629. doi: 10.1007/s13238-020-00708-8
Cellular metabolism and homeostasis in pluripotency regulation
Kun Liu, Jiani Cao, Xingxing Shi, Liang Wang, Tongbiao Zhao
2020, 11(9): 630-640. doi: 10.1007/s13238-020-00755-1
Pluripotent stem cells (PSCs) can immortally self-renew in culture with a high proliferation rate, and they possess unique metabolic characteristics that facilitate pluripotency regulation. Here, we review recent progress in understanding the mechanisms that link cellular metabolism and homeostasis to pluripotency regulation, with particular emphasis on pathways involving amino acid metabolism, lipid metabolism, the ubiquitin-proteasome system and autophagy. Metabolism of amino acids and lipids is tightly coupled to epigenetic modification, organelle remodeling and cell signaling pathways for pluripotency regulation. PSCs harness enhanced proteasome and autophagy activity to meet the material and energy requirements for cellular homeostasis. These regulatory events reflect a fine balance between the intrinsic cellular requirements and the extrinsic environment. A more complete understanding of this balance will pave new ways to manipulate PSC fate.
Research articles
Live cell imaging and proteomic profiling of endogenous NEAT1 lncRNA by CRISPR/Cas9-mediated knock-in
Bohong Chen, Shengcheng Deng, Tianyu Ge, Miaoman Ye, Jianping Yu, Song Lin, Wenbin Ma, Zhou Songyang
2020, 11(9): 641-660. doi: 10.1007/s13238-020-00706-w
In mammalian cells, long noncoding RNAs (lncRNAs) form complexes with proteins to execute various biological functions such as gene transcription, RNA processing and other signaling activities. However, methods to track endogenous lncRNA dynamics in live cells and screen for lncRNA interacting proteins are limited. Here, we report the development of CERTIS (CRISPR-mediated Endogenous lncRNA Tracking and Immunoprecipitation System) to visualize and isolate endogenous lncRNA, by precisely inserting a 24-repeat MS2 tag into the distal end of lncRNA locus through the CRISPR/Cas9 technology. In this study, we show that CERTIS effectively labeled the paraspeckle lncRNA NEAT1 without disturbing its physiological properties and could monitor the endogenous expression variation of NEAT1. In addition, CERTIS displayed superior performance on both short- and long-term tracking of NEAT1 dynamics in live cells. We found that NEAT1 and paraspeckles were sensitive to topoisomerase I specific inhibitors. Moreover, RNA Immunoprecipitation (RIP) of the MS2-tagged NEAT1 lncRNA successfully revealed several new protein components of paraspeckle. Our results support CERTIS as a tool suitable to track both spatial and temporal lncRNA regulation in live cells as well as study the lncRNA-protein interactomes.
BMAL1 regulates mitochondrial fission and mitophagy through mitochondrial protein BNIP3 and is critical in the development of dilated cardiomyopathy
Ermin Li, Xiuya Li, Jie Huang, Chen Xu, Qianqian Liang, Kehan Ren, Aobing Bai, Chao Lu, Ruizhe Qian, Ning Sun
2020, 11(9): 661-679. doi: 10.1007/s13238-020-00713-x
Dysregulation of circadian rhythms associates with cardiovascular disorders. It is known that deletion of the core circadian gene Bmal1 in mice causes dilated cardiomyopathy. However, the biological rhythm regulation system in mouse is very different from that of humans. Whether BMAL1 plays a role in regulating human heart function remains unclear. Here we generated a BMAL1 knockout human embryonic stem cell (hESC) model and further derived human BMAL1 deficient cardiomyocytes. We show that BMAL1 deficient hESC-derived cardiomyocytes exhibited typical phenotypes of dilated cardiomyopathy including attenuated contractility, calcium dysregulation, and disorganized myofilaments. In addition, mitochondrial fission and mitophagy were suppressed in BMAL1 deficient hESC-cardiomyocytes, which resulted in significantly attenuated mitochondrial oxidative phosphorylation and compromised cardiomyocyte function. We also found that BMAL1 binds to the E-box element in the promoter region of BNIP3 gene and specifically controls BNIP3 protein expression. BMAL1 knockout directly reduced BNIP3 protein level, causing compromised mitophagy and mitochondria dysfunction and thereby leading to compromised cardiomyocyte function. Our data indicated that the core circadian gene BMAL1 is critical for normal mitochondria activities and cardiac function. Circadian rhythm disruption may directly link to compromised heart function and dilated cardiomyopathy in humans.
Single-cell analysis reveals bronchoalveolar epithelial dysfunction in COVID-19 patients
Jiangping He, Shuijiang Cai, Huijian Feng, Baomei Cai, Lihui Lin, Yuanbang Mai, Yinqiang Fan, Airu Zhu, Huang Huang, Junjie Shi, Dingxin Li, Yuanjie Wei, Yueping Li, Yingying Zhao, Yuejun Pan, He Liu, Xiaoneng Mo, Xi He, Shangtao Cao, FengYu Hu, Jincun Zhao, Jie Wang, Nanshan Zhong, Xinwen Chen, Xilong Deng, Jiekai Chen
2020, 11(9): 680-687. doi: 10.1007/s13238-020-00752-4
ALKBH1 deficiency leads to loss of homeostasis in human diploid somatic cells
Hongyu Li, Zeming Wu, Xiaoqian Liu, Sheng Zhang, Qianzhao Ji, Xiaoyu Jiang, Zunpeng Liu, Si Wang, Jing Qu, Weiqi Zhang, Moshi Song, Eli Song, Guang-Hui Liu
2020, 11(9): 688-695. doi: 10.1007/s13238-020-00744-4
Correction to: Core transcriptional signatures of phase change in the migratory locust
Pengcheng Yang, Li Hou, Xianhui Wang, Le Kang
2020, 11(9): 696-697. doi: 10.1007/s13238-019-00688-4