2022 Vol. 13, No. 8

The embryonic stem cells (ESCs) have become as an important tool for studying cellular activities and biological events based on their self-renewal ability and in vitro/in vivo developmental potentials. While, maintaining the genome integrity is crucial for these characteristics. In this issue, Wang et al. demonstrated the irreplaceable role of BMP4 in sustaining chromosomal integrity and pluripotency of mESCs in the serum-free condition. Chromosomal stability is as important as roots to a tree. The roots must be strong and intact to nourish the sapling to grow into a towering tree with dazzling flowers. This cover is designed by Mingzhu Wang and Kun Zhao, and illustrated by Ling Jin.

Legacy of Hongxi Su: Pioneer of Chinese Cardiosurgery
Sumin Yang, Haoyu Hu, Xin Zheng, Shizhong Wang, Li Yuan
2022, 13(8): 549-551. doi: 10.1007/s13238-021-00848-5
Policy Forum
A framework for the responsible reform of the 14-day rule in human embryo research
Yaojin Peng, Jianwei Lv, Zhenyu Xiao, Lulu Ding, Qi Zhou
2022, 13(8): 552-558. doi: 10.1007/s13238-022-00907-5
Emerging roles of spliceosome in cancer and immunity
Hui Yang, Bruce Beutler, Duanwu Zhang
2022, 13(8): 559-579. doi: 10.1007/s13238-021-00856-5
Precursor messenger RNA (pre-mRNA) splicing is catalyzed by an intricate ribonucleoprotein complex called the spliceosome. Although the spliceosome is considered to be general cell “housekeeping” machinery, mutations in core components of the spliceosome frequently correlate with cell- or tissue-specific phenotypes and diseases. In this review, we expound the links between spliceosome mutations, aberrant splicing, and human cancers. Remarkably, spliceosome-targeted therapies (STTs) have become efficient anti-cancer strategies for cancer patients with splicing defects. We also highlight the links between spliceosome and immune signaling. Recent studies have shown that some spliceosome gene mutations can result in immune dysregulation and notable phenotypes due to mis-splicing of immune-related genes. Furthermore, several core spliceosome components harbor splicing-independent immune functions within the cell, expanding the functional repertoire of these diverse proteins.
Research Articles
BMP4 preserves the developmental potential of mESCs through Ube2s- and Chmp4b-mediated chromosomal stability safeguarding
Mingzhu Wang, Kun Zhao, Meng Liu, Mengting Wang, Zhibin Qiao, Shanru Yi, Yonghua Jiang, Xiaochen Kou, Yanhong Zhao, Jiqing Yin, Tianming Li, Hong Wang, Cizhong Jiang, Shaorong Gao, Jiayu Chen
2022, 13(8): 580-601. doi: 10.1007/s13238-021-00896-x
Chemically defined medium is widely used for culturing mouse embryonic stem cells (mESCs), in which N2B27 works as a substitution for serum, and GSK3β and MEK inhibitors (2i) help to promote ground-state pluripotency. However, recent studies suggested that MEKi might cause irreversible defects that compromise the developmental potential of mESCs. Here, we demonstrated the deficient bone morphogenetic protein (BMP) signal in the chemically defined condition is one of the main causes for the impaired pluripotency. Mechanistically, activating the BMP signal pathway by BMP4 could safeguard the chromosomal integrity and proliferation capacity of mESCs through regulating downstream targets Ube2s and Chmp4b. More importantly, BMP4 promotes a distinct in vivo developmental potential and a long-term pluripotency preservation. Besides, the pluripotent improvements driven by BMP4 are superior to those by attenuating MEK suppression. Taken together, our study shows appropriate activation of BMP signal is essential for regulating functional pluripotency and reveals that BMP4 should be applied in the serum-free culture system.
SARS-CoV-2 impairs the disassembly of stress granules and promotes ALS-associated amyloid aggregation
Yichen Li, Shuaiyao Lu, Jinge Gu, Wencheng Xia, Shengnan Zhang, Shenqing Zhang, Yan Wang, Chong Zhang, Yunpeng Sun, Jian Lei, Cong Liu, Zhaoming Su, Juntao Yang, Xiaozhong Peng, Dan Li
2022, 13(8): 602-614. doi: 10.1007/s13238-022-00905-7
The nucleocapsid (N) protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation, which enables its incorporation into stress granules (SGs) of host cells. However, whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow, neither do we know its consequence. Here, we used SARS-CoV-2 to infect mammalian cells and observed the incorporation of N protein into SGs, which resulted in markedly impaired self-disassembly but stimulated cell cellular clearance of SGs. NMR experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific transient interactions, which not only expedites the phase transition of these proteins to aberrant amyloid aggregation in vitro, but also promotes the aggregation of FUS with ALS-associated P525L mutation in cells. In addition, we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian cells. Our work indicates that SARS-CoV-2 infection can impair the disassembly of host SGs and promote the aggregation of SG-related amyloid proteins, which may lead to an increased risk of neurodegeneration.
Hyperthermia differentially affects specific human stem cells and their differentiated derivatives
Si Wang, Fang Cheng, Qianzhao Ji, Moshi Song, Zeming Wu, Yiyuan Zhang, Zhejun Ji, Huyi Feng, Juan Carlos Izpisua Belmonte, Qi Zhou, Jing Qu, Wei Li, Guang-Hui Liu, Weiqi Zhang
2022, 13(8): 615-622. doi: 10.1007/s13238-021-00887-y
Correction to: Rescue of premature aging defects in Cockayne syndrome stem cells by CRISPR/Cas9-mediated gene correction
Si Wang, Zheying Min, Qianzhao Ji, Lingling Geng, Yao Su, Zunpeng Liu, Huifang Hu, Lixia Wang, Weiqi Zhang, Keiichiro Suzuiki, Yu Huang, Puyao Zhang, Tie-Shan Tang, Jing Qu, Yang Yu, Guang-Hui Liu, Jie Qiao
2022, 13(8): 623-625. doi: 10.1007/s13238-021-00901-3