2022 Vol. 13, No. 7

RNA binding protein LIN28A is mainly localized in the nucleolus in early embryo development, and it can reside in a complex containing NCL and TRIM28 to repress Dux and promote rRNA expression. Meanwhile, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to ribosomal stress and activation of p53 which in turn binds to and activates 2C transcription factor Dux. LIN28 is a crucial factor to bridge two adjacent processes after ZGA: on one hand, LIN28 shuts down the 2-cell/4-cell program, and on the other hand, LIN28 promotes a pro-proliferation and anabolic program and a shift away from the 2C-like state with a metabolically inactive and translationally inert program.

Chia Chi Wang and his research on Protozoology
Ting Shi, Lei Fu
2022, 13(7): 473-475. doi: 10.1007/s13238-020-00759-x
Therapeutic cell engineering: designing programmable synthetic genetic circuits in mammalian cells
Maysam Mansouri, Martin Fussenegger
2022, 13(7): 476-489. doi: 10.1007/s13238-021-00876-1
Cell therapy approaches that employ engineered mammalian cells for on-demand production of therapeutic agents in the patient's body are moving beyond proof-of-concept in translational medicine. The therapeutic cells can be customized to sense user-defined signals, process them, and respond in a programmable and predictable way. In this paper, we introduce the available tools and strategies employed to design therapeutic cells. Then, various approaches to control cell behaviors, including open-loop and closed-loop systems, are discussed. We also highlight therapeutic applications of engineered cells for early diagnosis and treatment of various diseases in the clinic and in experimental disease models. Finally, we consider emerging technologies such as digital devices and their potential for incorporation into future cell-based therapies.
Research Article
LIN28 coordinately promotes nucleolar/ribosomal functions and represses the 2C-like transcriptional program in pluripotent stem cells
Zhen Sun, Hua Yu, Jing Zhao, Tianyu Tan, Hongru Pan, Yuqing Zhu, Lang Chen, Cheng Zhang, Li Zhang, Anhua Lei, Yuyan Xu, Xianju Bi, Xin Huang, Bo Gao, Longfei Wang, Cristina Correia, Ming Chen, Qiming Sun, Yu Feng, Li Shen, Hao Wu, Jianlong Wang, Xiaohua Shen, George Q. Daley, Hu Li, Jin Zhang
2022, 13(7): 490-512. doi: 10.1007/s13238-021-00864-5
LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Genomic and transcriptomic analysis unveils population evolution and development of pesticide resistance in fall armyworm Spodoptera frugiperda
Furong Gui, Tianming Lan, Yue Zhao, Wei Guo, Yang Dong, Dongming Fang, Huan Liu, Haimeng Li, Hongli Wang, Ruoshi Hao, Xiaofang Cheng, Yahong Li, Pengcheng Yang, Sunil Kumar Sahu, Yaping Chen, Le Cheng, Shuqi He, Ping Liu, Guangyi Fan, Haorong Lu, Guohai Hu, Wei Dong, Bin Chen, Yuan Jiang, Yongwei Zhang, Hanhong Xu, Fei Lin, Bernard Slippers, Alisa Postma, Matthew Jackson, Birhan Addisie Abate, Kassahun Tesfaye, Aschalew Lemma Demie, Meseret Destaw Bayeleygne, Dawit Tesfaye Degefu, Feng Chen, Paul K. Kuria, Zachary M. Kinyua, Tong-Xian Liu, Huanming Yang, Fangneng Huang, Xin Liu, Jun Sheng, Le Kang
2022, 13(7): 513-531. doi: 10.1007/s13238-020-00795-7
The fall armyworm (FAW), Spodoptera frugiperda, is a destructive pest native to America and has recently become an invasive insect pest in China. Because of its rapid spread and great risks in China, understanding of FAW genetic background and pesticide resistance is urgent and essential to develop effective management strategies. Here, we assembled a chromosome-level genome of a male FAW (SFynMstLFR) and compared re-sequencing results of the populations from America, Africa, and China. Strain identification of 163 individuals collected from America, Africa and China showed that both C and R strains were found in the American populations, while only C strain was found in the Chinese and African populations. Moreover, population genomics analysis showed that populations from Africa and China have close relationship with significantly genetic differentiation from American populations. Taken together, FAWs invaded into China were most likely originated from Africa. Comparative genomics analysis displayed that the cytochrome p450 gene family is extremely expanded to 425 members in FAW, of which 283 genes are specific to FAW. Treatments of Chinese populations with twenty-three pesticides showed the variant patterns of transcriptome profiles, and several detoxification genes such as AOX, UGT and GST specially responded to the pesticides. These findings will be useful in developing effective strategies for management of FAW in China and other invaded areas.
Large-scale chemical screen identifies Gallic acid as a geroprotector for human stem cells
Hezhen Shan, Lingling Geng, Xiaoyu Jiang, Moshi Song, Jianxun Wang, Zunpeng Liu, Xiao Zhuo, Zeming Wu, Jianli Hu, Zhejun Ji, Si Wang, Piu Chan, Jing Qu, Weiqi Zhang, Guang-Hui Liu
2022, 13(7): 532-539. doi: 10.1007/s13238-021-00872-5
Single-cell RNA sequencing reveals B cell-T cell interactions in vascular adventitia of hyperhomocysteinemia-accelerated atherosclerosis
Xiaolong Ma, Jiacheng Deng, Lulu Han, Yuwei Song, Yutong Miao, Xing Du, Guohui Dang, Dongmin Yang, Bitao Zhong, Changtao Jiang, Wei Kong, Qingbo Xu, Juan Feng, Xian Wang
2022, 13(7): 540-547. doi: 10.1007/s13238-021-00904-0