Journal of Genetics and Genomics

The advancements, challenges, and future implications of the CRISPR/Cas9 system in swine research

Jinfu Zhang, Emmanuel M. Khazalwa, Hussein M. Abkallo, Yuan Zhou, Xiongwei Nie, Jinxue Ruan, Changzhi Zhao, Jieru Wang, Jing Xu, Xinyun Li, Shuhong Zhao, Erwei Zuo, Lucilla Steinaa, Shengsong Xie

2021, 48(5): 347-360. doi: 10.1016/j.jgg.2021.03.015

Abstract (229) PDF (19)

Abstract:
Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) genome editing technology has dramatically influenced swine research by enabling the production of high-quality disease-resistant pig breeds, thus improving yields. In addition, CRISPR/Cas9 has been used extensively in pigs as one of the tools in biomedical research. In this review, we present the advancements of the CRISPR/Cas9 system in swine research, such as animal breeding, vaccine development, xenotransplantation, and disease modeling. We also highlight the current challenges and some potential applications of the CRISPR/Cas9 technologies.

Immu-Mela: An open resource for exploring immunotherapy-related multidimensional genomic profiles in melanoma

Jing Yang, Shilin Zhao, Jing Wang, Quanhu Sheng, Qi Liu, Yu Shyr

2021, 48(5): 361-368. doi: 10.1016/j.jgg.2021.03.016

Abstract (193) HTML PDF (8)

Abstract:
There are increasing studies aimed to reveal genomic hallmarks predictive of immune checkpoint blockade (ICB) treatment response, which generated a large number of data and provided an unprecedented opportunity to identify response-related features and evaluate their robustness across cohorts. However, those valuable data sets are not easily accessible to the research community. To take full advantage of existing large-scale immuno-genomic profiles, we developed Immu-Mela (http://bioinfo.vanderbilt.edu/database/Immu-Mela/), a multidimensional immuno-genomic portal that provides interactive exploration of associations between ICB responsiveness and multi-omics features in melanoma, including genetic, transcriptomics, immune cells, and single-cell populations. Immu-Mela also enables integrative analysis of any two genomic features. We demonstrated the value of Immu-Mela by identifying known and novel genomic features associated with ICB response. In addition, Immu-Mela allows users to upload their data sets (unrestricted to any cancer types) and co-analyze with existing data to identify and validate signatures of interest. Immu-Mela reduces barriers between researchers and complex genomic data, facilitating discoveries in cancer immunotherapy.

Arabidopsis RPD3-like histone deacetylases form multiple complexes involved in stress response

Chao Feng, Xue-Wei Cai, Yin-Na Su, Lin Li, She Chen, Xin-Jian He

2021, 48(5): 369-383. doi: 10.1016/j.jgg.2021.04.004

Abstract (258) HTML PDF (40)

Abstract:
The Arabidopsis thaliana RPD3-type histone deacetylases have been known to form conserved SIN3-type histone deacetylase complexes, but whether they form other types of complexes is unknown. Here, we perform affinity purification followed by mass spectrometry and demonstrate that the Arabidopsis RPD3-type histone deacetylases HDA6 and HDA19 interact with several previously uncharacterized proteins, thereby forming three types of plant-specific histone deacetylase complexes, which we named SANT, ESANT, and ARID. RNA-seq indicates that the newly identified components function together with HDA6 and HDA19 and coregulate the expression of a number of genes. HDA6 and HDA19 were previously thought to repress gene transcription by histone deacetylation. We find that the histone deacetylase complexes can repress gene expression via both histone deacetylation-dependent and -independent mechanisms. In the mutants of histone deacetylase complexes, the expression of a number of stress-induced genes is up-regulated, and several mutants of the histone deacetylase complexes show severe retardation in growth. Considering that growth retardation is thought to be a trade-off for an increase in stress tolerance, we infer that the histone deacetylase complexes identified in this study prevent over-expression of stress-induced genes and thereby ensure normal growth of plants under nonstress conditions.

Ufl1 deficiency causes kidney atrophy associated with disruption of endoplasmic reticulum homeostasis

You Zhou, Xifu Ye, Chenlu Zhang, Jiabao Wang, Zeyuan Guan, Juzhen Yan, Lu Xu, Ke Wang, Di Guan, Qian Liang, Jian Mao, Junzhi Zhou, Qian Zhang, Xiaoying Wu, Miao Wang, Yu-Sheng Cong, Jiang Liu

2021, 48(5): 403-410. doi: 10.1016/j.jgg.2021.04.006

Abstract (122) HTML PDF (17)

Abstract:
The UFMylation modification is a novel ubiquitin-like conjugation system, consisting of UBA5 (E1), UFC1 (E2), UFL1 (E3), and the conjugating molecule UFM1. Deficiency in this modification leads to embryonic lethality in mice and diseases in humans. However, the function of UFL1 is poorly characterized. Studies on Ufl1 conditional knockout mice have demonstrated that the deletion of Ufl1 in cardiomyocytes and in intestinal epithelial cells causes heart failure and increases susceptibility to experimentally induced colitis, respectively, suggesting an essential role of UFL1 in the maintenance of the homeostasis in these organs. Yet, its physiological function in other tissues and organs remains completely unknown. In this study, we generate the nephron tubules specific Ufl1 knockout mice and find that the absence of Ufl1 in renal tubular results in kidney atrophy and interstitial fibrosis. In addition, Ufl1 deficiency causes the activation of unfolded protein response and cell apoptosis, which may be responsible for the kidney atrophy and interstitial fibrosis. Collectively, our results have demonstrated the crucial role of UFL1 in regulating kidney function and maintenance of endoplasmic reticulum homeostasis, providing another layer of understanding kidney atrophy.

Transcriptomic profiling of tumor microenvironment reveals distinct immune subgroups of metastatic melanoma and its potential implications for immunotherapy

Yixuan Huang, Peng Zhang

2021, 48(5): 426-428. doi: 10.1016/j.jgg.2021.03.008

Abstract (162) HTML PDF (17)

Abstract:

2021 Vol. 48, No. 5