p53 inhibits CRISPR-Cas9 engineering in human pluripotent stem cells (Record no. 51306)
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| fixed length control field | 02136nam a2200253Ia 4500 |
| 003 - CONTROL NUMBER IDENTIFIER | |
| control field | MX-MdCICY |
| 005 - DATE AND TIME OF LATEST TRANSACTION | |
| control field | 20250625160205.0 |
| 040 ## - CATALOGING SOURCE | |
| Transcribing agency | CICY |
| 090 ## - LOCALLY ASSIGNED LC-TYPE CALL NUMBER (OCLC); LOCAL CALL NUMBER (RLIN) | |
| Classification number (OCLC) (R) ; Classification number, CALL (RLIN) (NR) | B-17143 |
| 008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION | |
| fixed length control field | 250602s9999 xx |||||s2 |||| ||und|d |
| 245 10 - TITLE STATEMENT | |
| Title | p53 inhibits CRISPR-Cas9 engineering in human pluripotent stem cells |
| 490 0# - SERIES STATEMENT | |
| Volume/sequential designation | Nature Medicine, 24, p.939-946, 2018 |
| 520 3# - SUMMARY, ETC. | |
| Summary, etc. | CRISPR/Cas9 has revolutionized our ability to engineer genomes and conduct genome-wide screens in human cells1,2,3. Whereas some cell types are amenable to genome engineering, genomes of human pluripotent stem cells (hPSCs)have been difficult to engineer, with reduced efficiencies relative to tumour cell lines or mouse embryonic stem cells3,4,5,6,7,8,9,10,11,12,13. Here, using hPSC lines with stable integration of Cas9 or transient delivery of Cas9-ribonucleoproteins (RNPs), we achieved an average insertion or deletion (indel)efficiency greater than 80 percent. This high efficiency of indel generation revealed that double-strand breaks (DSBs)induced by Cas9 are toxic and kill most hPSCs. In previous studies, the toxicity of Cas9 in hPSCs was less apparent because of low transfection efficiency and subsequently low DSB induction3. The toxic response to DSBs was P53/TP53-dependent, such that the efficiency of precise genome engineering in hPSCs with a wild-type P53 gene was severely reduced. Our results indicate that Cas9 toxicity creates an obstacle to the high-throughput use of CRISPR/Cas9 for genome engineering and screening in hPSCs. Moreover, as hPSCs can acquire P53 mutations14, cell replacement therapies using CRISPR/Cas9-enginereed hPSCs should proceed with caution, and such engineered hPSCs should be monitored for P53 function. |
| 650 14 - SUBJECT ADDED ENTRY--TOPICAL TERM | |
| Topical term or geographic name entry element | CRISPR-CAS9 |
| 700 12 - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Ihry, R. J. |
| 700 12 - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Worringer, K. A. |
| 700 12 - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Salick, M. R. |
| 700 12 - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Frias, E. |
| 700 12 - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Ho, D. |
| 700 12 - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Theriault, K. |
| 700 12 - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Randhawa, R. |
| 856 40 - ELECTRONIC LOCATION AND ACCESS | |
| Uniform Resource Identifier | <a href="https://drive.google.com/file/d/1vbptoMB4_eTjMHay131FGNrUwPVYDL8X/view?usp=drivesdk">https://drive.google.com/file/d/1vbptoMB4_eTjMHay131FGNrUwPVYDL8X/view?usp=drivesdk</a> |
| Public note | Para ver el documento ingresa a Google con tu cuenta: @cicy.edu.mx |
| 942 ## - ADDED ENTRY ELEMENTS (KOHA) | |
| Source of classification or shelving scheme | Clasificación local |
| Koha item type | Documentos solicitados |
| Lost status | Source of classification or shelving scheme | Damaged status | Not for loan | Collection | Home library | Current library | Shelving location | Date acquired | Total checkouts | Full call number | Date last seen | Price effective from | Koha item type |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Clasificación local | Ref1 | CICY | CICY | Documento préstamo interbibliotecario | 25.06.2025 | B-17143 | 25.06.2025 | 25.06.2025 | Documentos solicitados |