Transcriptomics

Dataset Information

0

RNA-seq of expanded human CRISPR/HDR-mediated FOXP3-KO naive Tregs, Cas9 naive Tregs, and conventional T cells


ABSTRACT: Treg cell therapy is a promising curative approach for a variety of immune-mediated conditions. CRISPR-based genome editing allows precise insertion of transgenes through homology-directed repair, but its use in human Tregs has been limited. We report an optimized protocol for CRISPR-mediated gene knock-in in human Tregs with high-yield expansion. To establish a benchmark of human Treg dysfunction, we target the master transcription factor FOXP3 in naive and memory Tregs. Although FOXP3-ablated Tregs upregulate cytokine expression, effects on suppressive capacity in vitro manifest slowly and primarily in memory Tregs. Moreover, FOXP3-ablated Tregs retain their characteristic protein, transcriptional, and DNA methylation profile. Instead, FOXP3 maintains DNA methylation at regions enriched for AP-1 binding sites. Thus, while FOXP3 is important for human Treg development, it has a limited role in maintaining mature Treg identity. Optimized gene knock-in with human Tregs will enable mechanistic studies and the development of tailored, next-generation Treg cell therapies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE176191 | GEO | 2021/08/03

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2021-08-03 | GSE164149 | GEO
2008-10-21 | E-GEOD-11818 | biostudies-arrayexpress
2014-12-12 | E-GEOD-56299 | biostudies-arrayexpress
2008-06-20 | GSE11818 | GEO
2016-01-19 | E-GEOD-76598 | biostudies-arrayexpress
2015-11-01 | E-GEOD-63455 | biostudies-arrayexpress
| PRJNA735242 | ENA
2014-11-05 | E-GEOD-62964 | biostudies-arrayexpress
2021-04-29 | GSE164548 | GEO
2015-04-30 | E-GEOD-61834 | biostudies-arrayexpress