Identification of potential chemical compounds enhancing generation of enucleated cells from immortalized human erythroid cell lines
(2021) In Communications Biology 4(1).- 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... (More)
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.
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- author
- Soboleva, Svetlana LU ; Kurita, Ryo ; Ek, Fredrik LU ; Åkerstrand, Hugo LU ; Silvério-Alves, Rita LU ; Olsson, Roger LU ; Nakamura, Yukio and Miharada, Kenichi LU
- organization
-
- Stem Cell Metabolism (research group)
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
- LUCC: Lund University Cancer Centre
- Chemical Biology and Therapeutics (research group)
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
- NanoLund: Centre for Nanoscience
- Developmental Immunology (research group)
- Cell Reprogramming in Hematopoiesis and Immunity (research group)
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Communications Biology
- volume
- 4
- issue
- 1
- article number
- 677
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85107129875
- pmid:34083702
- ISSN
- 2399-3642
- DOI
- 10.1038/s42003-021-02202-1
- language
- English
- LU publication?
- yes
- id
- 02ce27f7-ac28-4cf8-ad6f-f6acda064b99
- date added to LUP
- 2021-06-18 12:45:30
- date last changed
- 2024-09-07 20:46:29
@article{02ce27f7-ac28-4cf8-ad6f-f6acda064b99, abstract = {{<p>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.</p>}}, author = {{Soboleva, Svetlana and Kurita, Ryo and Ek, Fredrik and Åkerstrand, Hugo and Silvério-Alves, Rita and Olsson, Roger and Nakamura, Yukio and Miharada, Kenichi}}, issn = {{2399-3642}}, language = {{eng}}, number = {{1}}, publisher = {{Nature Publishing Group}}, series = {{Communications Biology}}, title = {{Identification of potential chemical compounds enhancing generation of enucleated cells from immortalized human erythroid cell lines}}, url = {{http://dx.doi.org/10.1038/s42003-021-02202-1}}, doi = {{10.1038/s42003-021-02202-1}}, volume = {{4}}, year = {{2021}}, }