Renke Tan

All Publications

• Generation of induced pluripotent stem cell lines from patients with Emery-Dreifuss muscular dystrophy. Stem cell research Chorsi, M. S., Mui, B. J., Tan, R., Fernandez, H. M., Xu, L., Chao, J. T., Sampson, J. B., Wheeler, M. T., Wu, J. C. 2026; 91: 103926

  Abstract

  Emery-Dreifuss muscular dystrophy (EDMD) stems from pathogenic variants in LMNA. We generated two patient-specific iPSC lines from peripheral blood: SCVIi145-A carrying LMNA c.241T > C (p.Tyr81His) and SCVIi146-A carrying LMNA c.357-2A > G. Non-integrating Sendai reprogramming produced stable colonies that expressed undifferentiated human induced pluripotent stem cell (iPSC) state markers, cleared vector RNA by passage 16, and showed normal copy-number profiles by low-pass whole-genome sequencing (LP-WGS). Both lines matched donor STR profiles and formed ectoderm, mesoderm, and endoderm in directed differentiation. These lines enable studies of lamin-associated nuclear defects and support cardiac and skeletal muscle disease modeling.

  View details for DOI 10.1016/j.scr.2026.103926

  View details for PubMedID 41690201

• Generation of two induced pluripotent stem cell lines from dilated cardiomyopathy patients harbouring TTN mutations. Stem cell research Tan, R., Chen, Y. I., Zha, Y., Herron, T., Haddad, F., Sallam, K., Wu, J. C. 2025; 88: 103834

  Abstract

  Dilated cardiomyopathy (DCM) is a severe form of heart disease characterized by ventricular enlargement and impaired contractile function, often with a genetic basis. Truncating mutations in TTN, encoding the sarcomere protein titin, are one of the most common causes of DCM. To model titin-related DCM in vitro, we have established two human induced pluripotent stem cell (iPSC) lines from individuals who were diagnosed with DCM, each carrying a heterozygous truncating mutation within the TTN coding region. We have confirmed that both cell lines are normal in cell morphology, robustly express key pluripotency markers, maintain a normal diploid karyotype, and can differentiate into all three primary germ layers. These patient-specific iPSC lines represent an invaluable resource for investigating the complexity of titin-related cardiomyopathy.

  View details for DOI 10.1016/j.scr.2025.103834

  View details for PubMedID 40987017

• Advanced RPL19-TRAPKI-seq method reveals mechanism of action of bioactive compounds. Natural products and bioprospecting Zhu, D., Hu, J., Tan, R., Lin, X., Wang, R., Lu, J., Yu, B., Xie, Y., Ni, X., Liang, C., Dang, Y., Jiang, W. 2025; 15 (1): 16

  Abstract

  Natural products play a crucial role in new drug development, but their druggability is often limited by uncertain molecular targets and insufficient research on mechanisms of action. In this study, we developed a new RPL19-TRAPKI-seq method, combining CRISPR/Cas9 and TRAP technologies, to investigate these mechanisms. We identified and validated seven ribosomal large subunit surface proteins suitable for TRAP, selecting RPL19 for its high enrichment. We successfully established a stable cell line expressing EGFP-RPL19 using CRISPR knock-in and verified its efficiency and specificity in enriching ribosomes and translating mRNA. Integrated with next-generation sequencing, this method allows precise detection of translating mRNA. We validated RPL19-TRAPKI-seq by investigating rapamycin, an mTOR inhibitor, yielding results consistent with previous reports. This optimized TRAP technology provides an accurate representation of translating mRNA, closely reflecting protein expression levels. Furthermore, we investigated SBF-1, a 23-oxa-analog of natural saponin OSW-1 with significant anti-tumor activity but an unclear mechanism. Using RPL19-TRAPKI-seq, we found that SBF-1 exerts its cytotoxic effects on tumor cells by disturbing cellular oxidative phosphorylation. In conclusion, our method has been proven to be a promising tool that can reveal the mechanisms of small molecules with greater accuracy, setting the stage for future exploration of small molecules and advancing the fields of pharmacology and therapeutic development.

  View details for DOI 10.1007/s13659-025-00500-3

  View details for PubMedID 40042546

  View details for PubMedCentralID PMC11882491

• Snapshots of a tiny ancestral nuclease of Cas9. Trends in biochemical sciences Hou, Z., Tan, R., Zhang, Y. 2023; 48 (1): 9-10

  Abstract

  High-resolution structures solved by Schuler et al. shed light on how Cas9's evolutionary ancestor IscB operates as an RNA-guided nuclease. With only two-fifths the size of Cas9, IscB holds great promise for alleviating the cargo size constraint of in vivo CRISPR delivery.

  View details for DOI 10.1016/j.tibs.2022.08.008

  View details for PubMedID 36100522

• Nucleolus localization of SpyCas9 affects its stability and interferes with host protein translation in mammalian cells. Genes & diseases Tan, R., Du, W., Liu, Y., Cong, X., Bai, M., Jiang, C., Li, Z., Tan, M., Ma, D. K., Huang, Q., Jiang, W., Dang, Y. 2022; 9 (3): 731-740

  Abstract

  The CRISPR/Cas9 system, originally derived from the prokaryotic adaptive immune system, has been developed as efficient genome editing tools. It enables precise gene manipulation on chromosomal DNA through the specific binding of programmable sgRNA to target DNA, and the Cas9 protein, which has endonuclease activity, will cut a double strand break at specific locus. However, Cas9 is a foreign protein in mammalian cells, and the potential risks associated with its introduction into mammalian cells are not fully understood. In this study, we performed pull-down and mass spectrometry (MS) analysis of Streptococcus pyogenes Cas9 (SpyCas9) interacting proteins in HEK293T cells and showed that the majority of Cas9-associated proteins identified by MS were localized in the nucleolus. Interestingly, we further discovered that the Cas9 protein contains a sequence encoding a nucleolus detention signal (NoDS). Compared with wild-type (WT) Cas9, NoDS-mutated variants of Cas9 (mCas9) are less stable, although their gene editing activity is minimally affected. Overexpression of WT Cas9, but not mCas9, causes general effects on transcription and protein translation in the host cell. Overall, identification of NoDS in Cas9 will improve the understanding of Cas9's biological function in vivo, and the removal of NoDS in Cas9 may enhance its safety for future clinical use.

  View details for DOI 10.1016/j.gendis.2020.09.003

  View details for PubMedID 35782966

  View details for PubMedCentralID PMC9243344

• Cas11 enables genome engineering in human cells with compact CRISPR-Cas3 systems. Molecular cell Tan, R., Krueger, R. K., Gramelspacher, M. J., Zhou, X., Xiao, Y., Ke, A., Hou, Z., Zhang, Y. 2022; 82 (4): 852-867.e5

  Abstract

  Leading CRISPR-Cas technologies employ Cas9 and Cas12 enzymes that generate RNA-guided dsDNA breaks. Yet, the most abundant microbial adaptive immune systems, Type I CRISPRs, are under-exploited for eukaryotic applications. Here, we report the adoption of a minimal CRISPR-Cas3 from Neisseria lactamica (Nla) type I-C system to create targeted large deletions in the human genome. RNP delivery of its processive Cas3 nuclease and target recognition complex Cascade can confer ∼95% editing efficiency. Unexpectedly, NlaCascade assembly in bacteria requires internal translation of a hidden component Cas11 from within the cas8 gene. Furthermore, expressing a separately encoded NlaCas11 is the key to enable plasmid- and mRNA-based editing in human cells. Finally, we demonstrate that supplying cas11 is a universal strategy to systematically implement divergent I-C, I-D, and I-B CRISPR-Cas3 editors with compact sizes, distinct PAM preferences, and guide orthogonality. These findings greatly expand our ability to engineer long-range genome edits.

  View details for DOI 10.1016/j.molcel.2021.12.032

  View details for PubMedID 35051351

  View details for PubMedCentralID PMC8964063

• Continuous culture of urine-derived bladder cancer cells for precision medicine. Protein & cell Jiang, S., Wang, J., Yang, C., Tan, R., Hou, J., Shi, Y., Zhang, H., Ma, S., Wang, J., Zhang, M., Philips, G., Li, Z., Ma, J., Yu, W., Wang, G., Wu, Y., Schlegel, R., Wang, H., Cao, S., Guo, J., Liu, X., Dang, Y. 2019; 10 (12): 902-907

  View details for DOI 10.1007/s13238-019-0649-5

  View details for PubMedID 31347094

  View details for PubMedCentralID PMC6881267

• Targeting the N Terminus of eIF4AI for Inhibition of Its Catalytic Recycling. Cell chemical biology Jiang, C., Tang, Y., Ding, L., Tan, R., Li, X., Lu, J., Jiang, J., Cui, Z., Tang, Z., Li, W., Cao, Z., Schneider-Poetsch, T., Jiang, W., Luo, C., Ding, Y., Liu, J., Dang, Y. 2019; 26 (10): 1417-1426.e5

  Abstract

  DEAD-box ATP-dependent helicases (DEAH/D) are a family of conserved genes predominantly involved in gene expression regulation and RNA processing. As its prototype, eIF4AI is an essential component of the protein translation initiation complex. Utilizing a screening system based on wild-type eIF4AI and its L243G mutant with a changed linker domain, we discovered an eIF4AI inhibitor, sanguinarine (SAN) and used it to study the catalytic mechanism of eIF4AI. Herein, we describe the crystal structure of the eIF4AI-inhibitor complex and demonstrate that the binding site displays certain specificity, which can provide the basis for drug design to target eIF4AI. We report that except for competitive inhibition SAN's possible mechanism of action involves interference with eIF4AI catalytic cycling process by hindering the formation of the closed conformation of eIF4AI. In addition, our results highlight a new targetable site on eIF4AI and confirm eIF4AI as a viable pharmacological target.

  View details for DOI 10.1016/j.chembiol.2019.07.010

  View details for PubMedID 31402318

• Prolyl 4-hydroxylase 2 promotes B-cell lymphoma progression via hydroxylation of Carabin. Blood Jiang, W., Zhou, X., Li, Z., Liu, K., Wang, W., Tan, R., Cong, X., Shan, J., Zhan, Y., Cui, Z., Jiang, L., Li, Q., Shen, S., Bai, M., Cheng, Y., Li, B., Tan, M., Ma, D. K., Liu, J. O., Dang, Y. 2018; 131 (12): 1325-1336

  Abstract

  B-cell lymphomas are heterogeneous blood disorders with limited therapeutic options, largely because of their propensity to relapse and become refractory to treatments. Carabin, a key suppressor of B-cell receptor signaling and proliferation, is inactivated in B-cell lymphoma by unknown mechanisms. Here, we identify prolyl 4-hydroxylase 2 (P4HA2) as a specific proline hydroxylase of Carabin. Carabin hydroxylation leads to its proteasomal degradation, thereby activating the Ras/extracellular signal-regulated kinase pathway and increasing B-cell lymphoma proliferation. P4HA2 is undetectable in normal B cells but upregulated in the diffuse large B-cell lymphoma (DLBCL), driving Carabin inactivation and lymphoma proliferation. Our results indicate that P4HA2 is a potential prognosis marker for DLBCL and a promising pharmacological target for developing treatment of molecularly stratified B-cell lymphomas.

  View details for DOI 10.1182/blood-2017-07-794875

  View details for PubMedID 29437589

  View details for PubMedCentralID PMC5865229