TY - JOUR
T1 - Genetic programming of macrophages generates an in vitro model for the human erythroid island niche
AU - Lopez-Yrigoyen, Martha
AU - Yang, Cheng-Tao
AU - Fidanza, Antonella
AU - Cassetta, Luca
AU - Taylor, A. Helen
AU - McCahill, Angela
AU - Sellink, Erica
AU - von Lindern, Marieke
AU - van den Akker, Emile
AU - Mountford, Joanne C.
AU - Pollard, Jeffrey W.
AU - Forrester, Lesley M.
N1 - Funding Information: We thank Fiona Rossi and Claire Cryer for assistance with flow cytometry, Eoghan O’Duibhir and Bertrand Vernay with microscopy, Edinburgh Genomics and Jon Manning for RNA sequencing and analyses and James Bieker for critical comments on the manuscript. This work was funded by Wellcome Trust (102610) and Innovate UK (L.M.F., A.F. and A.H.T.), CONACYT (M.L.-Y.) and the Scottish Funding Council (C.-T.Y.). L.C. and J.W.P. were supported by Wellcome Trust (101067/Z/13/Z), Medical Research Council (MR/N022556/1), and COST Action BM1404 Mye-EUNITER (http://www.mye-euniter. eu) and E.S., E.v.d.A. and M.v.L were funded by ZONMW 40-41400-98-1327. Publisher Copyright: © 2019, The Author(s).
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85061827392&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30787325
U2 - https://doi.org/10.1038/s41467-019-08705-0
DO - https://doi.org/10.1038/s41467-019-08705-0
M3 - Article
C2 - 30787325
SN - 2041-1723
VL - 10
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 881
ER -