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Identification of potential chemical compounds enhancing generation of enucleated cells from immortalized human erythroid cell lines

Soboleva, Svetlana LU ; Kurita, Ryo ; Ek, Fredrik LU ; Åkerstrand, Hugo LU ; Silvério-Alves, Rita LU ; Olsson, Roger LU orcid ; Nakamura, Yukio and Miharada, Kenichi LU (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
; ; ; ; ; ; and
organization
publishing date
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
2024-06-15 12:43:02
@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 &gt;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}},
}