Genetic programming of macrophages generates an in vitro model for the human erythroid island niche

Martha Lopez-Yrigoyen, Cheng-Tao Yang, Antonella Fidanza, Luca Cassetta, A. Helen Taylor, Angela McCahill, Erica Sellink, Marieke Lindern, Emile Akker, Joanne C. Mountford, Jeffrey W. Pollard and Lesley M. Forrester ()
Additional contact information
Martha Lopez-Yrigoyen: University of Edinburgh
Cheng-Tao Yang: University of Edinburgh
Antonella Fidanza: University of Edinburgh
Luca Cassetta: University of Edinburgh, Queens Medical Research Institute
A. Helen Taylor: University of Edinburgh
Angela McCahill: The Jack Copland Centre
Erica Sellink: The Netherlands and Landsteiner Laboratory
Marieke Lindern: The Netherlands and Landsteiner Laboratory
Emile Akker: The Netherlands and Landsteiner Laboratory
Joanne C. Mountford: The Jack Copland Centre
Jeffrey W. Pollard: University of Edinburgh, Queens Medical Research Institute
Lesley M. Forrester: University of Edinburgh

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: Abstract Red blood cells mature within the erythroblastic island (EI) niche that consists of specialized macrophages surrounded by differentiating erythroblasts. Here we establish an in vitro system to model the human EI niche using macrophages that are derived from human induced pluripotent stem cells (iPSCs), and are also genetically programmed to an EI-like phenotype by inducible activation of the transcription factor, KLF1. These EI-like macrophages increase the production of mature, enucleated erythroid cells from umbilical cord blood derived CD34+ haematopoietic progenitor cells and iPSCs; this enhanced production is partially retained even when the contact between progenitor cells and macrophages is inhibited, suggesting that KLF1-induced secreted proteins may be involved in this enhancement. Lastly, we find that the addition of three secreted factors, ANGPTL7, IL-33 and SERPINB2, significantly enhances the production of mature enucleated red blood cells. Our study thus contributes to the ultimate goal of replacing blood transfusion with a manufactured product.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-019-08705-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08705-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-08705-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().