Journal article
Single-cell assessment of transcriptome alterations induced by Scriptaid in early differentiated human haematopoietic progenitors during ex vivo expansion
- Abstract:
-
Priming haematopoietic stem/progenitor cells (HSPCs) in vitro with specific chromatin modifying agents and cytokines under serum-free-conditions significantly enhances engraftable HSC numbers. We extend these studies by culturing human CD133+ HSPCs on nanofibre scaffolds to mimic the niche for 5-days with the HDAC inhibitor Scriptaid and cytokines. Scriptaid increases absolute Lin−CD34+CD38−CD45RA−CD90+CD49f+ HSPC numbers, while concomitantly decreasing the Lin−CD38−CD34+CD45RA−CD90− subset. Hypothesising that Scriptaid plus cytokines expands the CD90+ subset without differentiation and upregulates CD90 on CD90− cells, we sorted, then cultured Lin−CD34+CD38−CD45RA−CD90− cells with Scriptaid and cytokines. Within 2-days and for at least 5-days, most CD90− cells became CD90+. There was no significant difference in the transcriptomic profile, by RNAsequencing, between cytokine-expanded and purified Lin−CD34+CD38−CD45RA−CD49f+CD90+ cells in the presence or absence of Scriptaid, suggesting that Scriptaid maintains stem cell gene expression programs despite expansion in HSC numbers. Supporting this, 50 genes were significantly differentially expressed between CD90+ and CD90− Lin−CD34+CD38−CD45RA−CD49f+ subsets in Scriptaid-cytokine- and cytokine only-expansion conditions. Thus, Scriptaid treatment of CD133+ cells may be a useful approach to expanding the absolute number of CD90+ HSC, without losing their stem cell characteristics, both through direct effects on HSC and potentially also conversion of their immediate CD90− progeny into CD90+ HSC.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
-
-
(Preview, Version of record, pdf, 2.4MB, Terms of use)
-
- Publisher copy:
- 10.1038/s41598-019-41803-z
Authors
- Publisher:
- Nature Research
- Journal:
- Scientific Reports More from this journal
- Volume:
- 9
- Article number:
- 5300
- Publication date:
- 2019-03-28
- Acceptance date:
- 2019-03-18
- DOI:
- EISSN:
-
2045-2322
- Pubs id:
-
pubs:984447
- UUID:
-
uuid:95a53cfe-dcae-4e71-b315-573ee1227a9d
- Local pid:
-
pubs:984447
- Source identifiers:
-
984447
- Deposit date:
-
2019-03-26
- ARK identifier:
Terms of use
- Copyright holder:
- Hua et al
- Copyright date:
- 2019
- Notes:
- © The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
If you are the owner of this record, you can report an update to it here: Report update to this record