4.6 Article

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

Journal

STEM CELL REPORTS
Volume 16, Issue 6, Pages 1629-1643

Publisher

CELL PRESS
DOI: 10.1016/j.stemcr.2021.04.010

Keywords

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Funding

  1. Stem Cells Australia, an Australian Research Council Special Research Initiative [SRI110001002]
  2. NHMRC Synergy [APP1186371]
  3. Wellcome Trust catalyst funding WELLCOME [097821/Z/11/B]
  4. Research into Inflammatory Arthritis Center Versus Arthritis (RACE) [20298]
  5. Versus Arthritis UK [20298, 22072]
  6. Center for Stem Cell Systems
  7. CSIRO Synthetic Biology Future Science Platform
  8. Australian Research Council [FT150100330]
  9. JEM Research Foundation
  10. Wellcome Trust [097821/Z/11/B] Funding Source: Wellcome Trust
  11. Australian Research Council [FT150100330] Funding Source: Australian Research Council

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The Stemformatics myeloid atlas provides an integrated transcriptome atlas of human macrophages and dendritic cells, comparing different sources of myeloid cells. The study found that culture significantly impacted primary cell phenotypes, and identified characteristic features in pluripotent stem cell-derived macrophages. The reproducibility of myeloid subsets and phenotypes across experimental series, including single-cell data, demonstrates the robust reference that the atlas provides.
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 from single-cell studies, demonstrating that the atlas provides a robust reference for myeloid phenotypes. Implementation in Stemformatics.org allows users to visualize patterns of sample grouping or gene expression for user-selected conditions and supports temporary upload of your own microarray or RNA sequencing samples, including single-cell data, to benchmark against the atlas.

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