Open AccessOptimised generation of iPSC-derived macrophages and dendritic cells that are functionally and transcriptionally similar to their primary counterparts
Author(s) -
Susan J. Monkley,
Jayendra Kumar Krishnaswamy,
Melker Göransson,
Maryam Clausen,
Johan Meuller,
Kristofer Thörn,
Ryan Hicks,
Stephen Delaney,
Louise Stjernborg
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0243807
Subject(s) - reprogramming , cd14 , induced pluripotent stem cell , biology , microbiology and biotechnology , monocyte , cellular differentiation , transcriptome , cell type , dendritic cell , macrophage , cell , gene expression , immunology , gene , in vitro , genetics , immune system , embryonic stem cell
Induced pluripotent stem cells (iPSC) offer the possibility to generate diverse disease-relevant cell types, from any genetic background with the use of cellular reprogramming and directed differentiation. This provides a powerful platform for disease modeling, drug screening and cell therapeutics. The critical question is how the differentiated iPSC-derived cells translate to their primary counterparts. Our refinement of a published differentiation protocol produces a CD14+ monocytic lineage at a higher yield, in a smaller format and at a lower cost. These iPSC-derived monocytes can be further differentiated into macrophages or dendritic cells (DC), both with similar morphological and functional profiles as compared to their primary counterparts. Transcriptomic analysis of iPSC-derived cells at different stages of differentiation as well as comparison to their blood-derived counterparts demonstrates a complete switch of iPSCs to cells expressing a monocyte, macrophage or DC specific gene profile. iPSC-derived macrophages respond to LPS treatment by inducing expression of classic macrophage pro-inflammatory response markers. Interestingly, though iPSC-derived DC show similarities to monocyte derived DC, they are more similar transcriptionally to a newly described subpopulation of AXL + DC. Thus, our study provides a detailed and accurate profile of iPSC-derived monocytic lineage cells.