2017 Vol. 8, No. 11

Dejun Yu: a patriotic botanist and his contributions
Hong Jiang
2017, 8(11): 785-787. doi: 10.1007/s13238-017-0381-y
Questions about horse spleen ferritin crossing the blood brain barrier via mouse transferrin receptor 1
Kelong Fan, Meng Zhou, Xiyun Yan
2017, 8(11): 788-790. doi: 10.1007/s13238-017-0481-8
Addressing challenges in the clinical applications associated with CRISPR/Cas9 technology and ethical questions to prevent its misuse
Xiang Jin Kang, Chiong Isabella Noelle Caparas, Boon Seng Soh, Yong Fan
2017, 8(11): 791-795. doi: 10.1007/s13238-017-0477-4
The lipid droplet: A conserved cellular organelle
Congyan Zhang, Pingsheng Liu
2017, 8(11): 796-800. doi: 10.1007/s13238-017-0467-6
The lipid droplet (LD) is a unique multi-functional organelle that contains a neutral lipid core covered with a phospholipid monolayer membrane. The LDs have been found in almost all organisms from bacteria to humans with similar shape. Several conserved functions of LDs have been revealed by recent studies, including lipid metabolism and trafficking, as well as nucleic acid binding and protection. We summarized these findings and proposed a hypothesis that the LD is a conserved organelle.
Cellular microparticles and pathophysiology of traumatic brain injury
Zilong Zhao, Yuan Zhou, Ye Tian, Min Li, Jing-fei Dong, Jianning Zhang
2017, 8(11): 801-810. doi: 10.1007/s13238-017-0414-6
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. The finding that cellular microparticles (MPs) generated by injured cells profoundly impact on pathological courses of TBI has paved the way for new diagnostic and therapeutic strategies. MPs are subcellular fragments or organelles that serve as carriers of lipids, adhesive receptors, cytokines, nucleic acids, and tissue-degrading enzymes that are unique to the parental cells. Their sub-micron sizes allow MPs to travel to areas that parental cells are unable to reach to exercise diverse biological functions. In this review, we summarize recent developments in identifying a casual role of MPs in the pathologies of TBI and suggest that MPs serve as a new class of therapeutic targets for the prevention and treatment of TBI and associated systemic complications.
Short article
Correction of β-thalassemia mutant by base editor in human embryos
Puping Liang, Chenhui Ding, Hongwei Sun, Xiaowei Xie, Yanwen Xu, Xiya Zhang, Ying Sun, Yuanyan Xiong, Wenbin Ma, Yongxiang Liu, Yali Wang, Jianpei Fang, Dan Liu, Zhou Songyang, Canquan Zhou, Junjiu Huang
2017, 8(11): 811-822. doi: 10.1007/s13238-017-0475-6
β-Thalassemia is a global health issue, caused by mutations in the HBB gene. Among these mutations, HBB -28 (A>G) mutations is one of the three most common mutations in China and Southeast Asia patients with β-thalassemia. Correcting this mutation in human embryos may prevent the disease being passed onto future generations and cure anemia. Here we report the first study using base editor (BE) system to correct disease mutant in human embryos. Firstly, we produced a 293T cell line with an exogenous HBB -28 (A>G) mutant fragment for gRNAs and targeting efficiency evaluation. Then we collected primary skin fibroblast cells from a β-thalassemia patient with HBB -28 (A>G) homozygous mutation. Data showed that base editor could precisely correct HBB -28 (A>G) mutation in the patient's primary cells. To model homozygous mutation disease embryos, we constructed nuclear transfer embryos by fusing the lymphocyte or skin fibroblast cells with enucleated in vitro matured (IVM) oocytes. Notably, the gene correction efficiency was over 23.0% in these embryos by base editor. Although these embryos were still mosaic, the percentage of repaired blastomeres was over 20.0%. In addition, we found that base editor variants, with narrowed deamination window, could promote G-to-A conversion at HBB -28 site precisely in human embryos. Collectively, this study demonstrated the feasibility of curing genetic disease in human somatic cells and embryos by base editor system.
Research articles
Recapitulating cortical development with organoid culture in vitro and modeling abnormal spindle-like (ASPM related primary) microcephaly disease
Rui Li, Le Sun, Ai Fang, Peng Li, Qian Wu, Xiaoqun Wang
2017, 8(11): 823-833. doi: 10.1007/s13238-017-0479-2
The development of a cerebral organoid culture in vitro offers an opportunity to generate human brain-like organs to investigate mechanisms of human disease that are specific to the neurogenesis of radial glial (RG) and outer radial glial (oRG) cells in the ventricular zone (VZ) and subventricular zone (SVZ) of the developing neocortex. Modeling neuronal progenitors and the organization that produces mature subcortical neuron subtypes during early stages of development is essential for studying human brain developmental diseases. Several previous efforts have shown to grow neural organoid in culture dishes successfully, however we demonstrate a new paradigm that recapitulates neocortical development process with VZ, OSVZ formation and the lamination organization of cortical layer structure. In addition, using patient-specific induced pluripotent stem cells (iPSCs) with dysfunction of the Aspm gene from a primary microcephaly patient, we demonstrate neurogenesis defects result in defective neuronal activity in patient organoids, suggesting a new strategy to study human developmental diseases in central nerve system.
Cryo-EM structures of the mammalian endo-lysosomal TRPML1 channel elucidate the combined regulation mechanism
Sensen Zhang, Ningning Li, Wenwen Zeng, Ning Gao, Maojun Yang
2017, 8(11): 834-847. doi: 10.1007/s13238-017-0476-5
TRPML1 channel is a non-selective group-2 transient receptor potential (TRP) channel with Ca2+ permeability. Located mainly in late endosome and lysosome of all mammalian cell types, TRPML1 is indispensable in the processes of endocytosis, membrane trafficking, and lysosome biogenesis. Mutations of TRPML1 cause a severe lysosomal storage disorder called mucolipidosis type IV (MLIV). In the present study, we determined the cryo-electron microscopy (cryo-EM) structures of Mus musculus TRPML1 (mTRPML1) in lipid nanodiscs and Amphipols. Two distinct states of mTRPML1 in Amphipols are added to the closed state, on which could represent two different confirmations upon activation and regulation. The polycystin-mucolipin domain (PMD) may sense the luminal/extracellular stimuli and undergo a "move upward" motion during endocytosis, thus triggering the overall conformational change in TRPML1. Based on the structural comparisons, we propose TRPML1 is regulated by pH, Ca2+, and phosphoinositides in a combined manner so as to accommodate the dynamic endocytosis process.
Using a novel cellular platform to optimize CRISPR/CAS9 technology for the gene therapy of AIDS
Jingjin He, Thanutra Zhang, Xuemei Fu
2017, 8(11): 848-852. doi: 10.1007/s13238-017-0453-z
Live cell imaging of genomic loci using dCas9-SunTag system and a bright fluorescent protein
Huiying Ye, Zhili Rong, Ying Lin
2017, 8(11): 853-855. doi: 10.1007/s13238-017-0460-0
The CARMA3-BCL10-MALT1 (CBM) complex contributes to DNA damage-induced NF-κB activation and cell survival
Shilei Zhang, Deng Pan, Xin-Ming Jia, Xin Lin, Xueqiang Zhao
2017, 8(11): 856-860. doi: 10.1007/s13238-017-0441-3