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一种化学方法有助于仅通过CRISPRa技术生成人类诱导多能干细胞，并将所需的靶向基因座数量降至最低。

A chemical approach facilitates CRISPRa-only human iPSC generation and minimizes the number of targeted loci required.

作者信息

Abujarour Ramzey, Dinella Jason, Pribadi Mochtar, Fong Lauren K, Denholtz Matthew, Gutierrez Alma, Haynes Matt, Mahmood Enaaya, Lee Tom T, Ding Sheng, Valamehr Bahram

机构信息

Fate Therapeutics, San Diego, CA 92121, USA.

School of Pharmaceutical Sciences, Tsinghua University, Beijing, China.

出版信息

Future Sci OA. 2024 May 15;10(1):FSO964. doi: 10.2144/fsoa-2023-0257. eCollection 2024.

DOI:10.2144/fsoa-2023-0257
PMID:38817352
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11137772/
Abstract

We explored the generation of human induced pluripotent stem cells (iPSCs) solely through the transcriptional activation of endogenous genes by CRISPR activation (CRISPRa). Minimal number of human-specific guide RNAs targeting a limited set of loci were used with a unique cocktail of small molecules (CRISPRa-SM). iPSC clones were efficiently generated by CRISPRa-SM, expressed general and naive iPSC markers and clustered with high-quality iPSCs generated using conventional reprogramming methods. iPSCs showed genomic stability and robust pluripotent potential as assessed by and . CRISPRa-SM-generated human iPSCs by direct and multiplexed loci activation facilitating a unique and potentially safer cellular reprogramming process to aid potential applications in cellular therapy and regenerative medicine.

摘要

我们探索了仅通过CRISPR激活（CRISPRa）内源性基因的转录激活来生成人类诱导多能干细胞（iPSC）。使用针对有限位点集的最少数量的人类特异性引导RNA与独特的小分子混合物（CRISPRa-SM）。CRISPRa-SM有效地产生了iPSC克隆，这些克隆表达了一般和原始的iPSC标志物，并与使用传统重编程方法产生的高质量iPSC聚集在一起。通过[具体评估方式1]和[具体评估方式2]评估，iPSC显示出基因组稳定性和强大的多能潜力。通过直接和多重位点激活产生的CRISPRa-SM人类iPSC促进了独特且可能更安全的细胞重编程过程，以辅助细胞治疗和再生医学中的潜在应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/514a/11137772/4b898d04d06c/IFSO_A_2340855_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/514a/11137772/8bcda6b144d2/IFSO_A_2340855_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/514a/11137772/b60983885dd9/IFSO_A_2340855_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/514a/11137772/13040eff90b3/IFSO_A_2340855_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/514a/11137772/4b898d04d06c/IFSO_A_2340855_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/514a/11137772/8bcda6b144d2/IFSO_A_2340855_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/514a/11137772/b60983885dd9/IFSO_A_2340855_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/514a/11137772/13040eff90b3/IFSO_A_2340855_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/514a/11137772/4b898d04d06c/IFSO_A_2340855_F0004_C.jpg

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2
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Semin Immunopathol. 2019 Jan;41(1):59-68. doi: 10.1007/s00281-018-0721-x. Epub 2018 Oct 25.
3
Human pluripotent reprogramming with CRISPR activators.利用 CRISPR 激活剂进行人类多能性重编程。
Nat Commun. 2018 Jul 6;9(1):2643. doi: 10.1038/s41467-018-05067-x.
4
CRISPR-Based Chromatin Remodeling of the Endogenous Oct4 or Sox2 Locus Enables Reprogramming to Pluripotency.基于 CRISPR 的内源性 Oct4 或 Sox2 基因座染色质重塑可实现重编程为多能性。
Cell Stem Cell. 2018 Feb 1;22(2):252-261.e4. doi: 10.1016/j.stem.2017.12.001. Epub 2018 Jan 18.
5
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Cell Reprogram. 2017 Jun;19(3):189-198. doi: 10.1089/cell.2017.0006.
6
Comparison of Cas9 activators in multiple species.多种物种中Cas9激活剂的比较。
Nat Methods. 2016 Jul;13(7):563-567. doi: 10.1038/nmeth.3871. Epub 2016 May 23.
7
Beyond editing: repurposing CRISPR-Cas9 for precision genome regulation and interrogation.超越编辑：重新利用CRISPR-Cas9进行精准基因组调控与探究。
Nat Rev Mol Cell Biol. 2016 Jan;17(1):5-15. doi: 10.1038/nrm.2015.2. Epub 2015 Dec 16.
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10
Highly efficient Cas9-mediated transcriptional programming.高效的Cas9介导的转录编程。
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