| RRC ID |
77818
|
| 著者 |
Soboleva S, Kurita R, Ek F, Åkerstrand H, Silvério-Alves R, Olsson R, Nakamura Y, Miharada K.
|
| タイトル |
Identification of potential chemical compounds enhancing generation of enucleated cells from immortalized human erythroid cell lines.
|
| ジャーナル |
Commun Biol
|
| Abstract |
Immortalized erythroid cell lines are expected to be a promising source of ex vivo manufactured red blood cells (RBCs), however the induction of enucleation in these cell lines is inefficient at present. We utilized an imaging-based high-throughput system to identify chemical compounds that trigger enucleation of human erythroid cell lines. Among >3,300 compounds, we identified multiple histone deacetylase inhibitors (HDACi) inducing enucleated cells from the cell line, although an increase in membrane fragility of enucleated cells was observed. Gene expression profiling revealed that HDACi treatment increased the expression of cytoskeletal genes, while an erythroid-specific cell membrane protein, SPTA1, was significantly down-regulated. Restoration of SPTA1 expression using CRISPR-activation partially rescued the fragility of cells and thereby improved the enucleation efficiency. Our observations provide a potential solution for the generation of mature cells from erythroid cell lines, contributing to the future realization of the use of immortalized cell lines for transfusion therapies.
|
| 巻・号 |
4(1)
|
| ページ |
677
|
| 公開日 |
2021-6-3
|
| DOI |
10.1038/s42003-021-02202-1
|
| PII |
10.1038/s42003-021-02202-1
|
| PMID |
34083702
|
| PMC |
PMC8175573
|
| MeSH |
Cell Differentiation / drug effects
Cell Differentiation / genetics
Cell Line
Cell Nucleus / drug effects*
Cell Nucleus / metabolism
Cell Survival / drug effects
Cell Survival / genetics
Cells, Cultured
Erythrocytes / cytology
Erythrocytes / metabolism*
Erythroid Cells / drug effects*
Erythroid Cells / metabolism
Gene Expression Profiling / methods*
High-Throughput Screening Assays / methods
Histone Deacetylase Inhibitors / isolation & purification
Histone Deacetylase Inhibitors / pharmacology*
Humans
Reverse Transcriptase Polymerase Chain Reaction
|
| IF |
4.165
|
| リソース情報 |
| ヒト・動物細胞 |
K562(RCB0027) |
