Journal article

An integrated analysis of human myeloid cells identifies gaps in in vitro models of in vivo biology

Nadia Rajab, Paul W Angel, Yidi Deng, Jennifer Gu, Vanta Jameson, Mariola Kurowska-Stolarska, Simon Milling, Chris M Pacheco, Matt Rutar, Andrew L Laslett, Kim-Anh Le Cao, Jarny Choi, Christine A Wells

STEM CELL REPORTS | CELL PRESS | Published : 2021

Abstract

The Stemformatics myeloid atlas is an integrated transcriptome atlas of human macrophages and dendritic cells that systematically compares freshly isolated tissue-resident, cultured, and pluripotent stem cell-derived myeloid cells. Three classes of tissue-resident macrophage were identified: Kupffer cells and microglia; monocyte-associated; and tumor-associated macrophages. Culture had a major impact on all primary cell phenotypes. Pluripotent stem cell-derived macrophages were characterized by atypical expression of collagen and a highly efferocytotic phenotype. Myeloid subsets, and phenotypes associated with derivation, were reproducible across experimental series including data projected ..

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Grants

Awarded by Stem Cells Australia, an Australian Research Council Special Research Initiative


Awarded by NHMRC Synergy


Awarded by Wellcome Trust catalyst funding WELLCOME


Awarded by Research into Inflammatory Arthritis Center Versus Arthritis (RACE)


Awarded by Versus Arthritis UK


Awarded by Australian Research Council


Funding Acknowledgements

The authors thank Tyrone Chen and Othmar Korn for assistance with data processing and Isha Nagpal for website development to support the Stemformatics interactive viewer. The authors thank Zahra Elahi for assistance in the annotation of samples. The authors thank Ramaciotti Center for Genomics (University of New South Wales; Sydney) and University of Glasgow Polyomics facilityfor mRNA sequencing, and the Melbourne Cytometry Platform for flow cytometry assistance. This work was funded by Stem Cells Australia, an Australian Research Council Special Research Initiative [SRI110001002] to C.A.W.; NHMRC Synergy [APP1186371] to C.A.W.; Wellcome Trust catalyst funding WELLCOME (097821/Z/11/B) to C.A.W., S.M., M.K.S.; S.M. work was supported by the Research into Inflammatory Arthritis Center Versus Arthritis (RACE) [#20298] ; M.K.S. is funded by Versus Arthritis UK [#20298 & #22072] . N.R. is funded by the Center for Stem Cell Systems and the CSIRO Synthetic Biology Future Science Platform. C.A.W. is funded by a Future Fellowship from the Australian Research Council [FT150100330] . J.C. is funded by the JEM Research Foundation to the Stem Cell Atlas.