1. An integrated analysis of human myeloid cells identifies gaps in in vitro models of in vivo biology
- Author
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Mariola Kurowska-Stolarska, Chris M. Pacheco, Kim-Anh Lê Cao, Paul W. Angel, Vanta Jameson, Yidi Deng, Jennifer Gu, Christine A. Wells, Simon Milling, Andrew L. Laslett, Jarny Choi, Nadia Rajab, and Matt Rutar
- Subjects
Resource ,tissue-resident macrophage ,Pluripotent Stem Cells ,0301 basic medicine ,pluripotent stem cell–derived macrophage ,Myeloid ,dendritic cell ,microglia ,Kupffer cell ,macrophage ,Computational biology ,Biology ,Biochemistry ,Regenerative medicine ,Monocytes ,Cell Line ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,medicine ,Humans ,Cells, Cultured ,hematopoietic progenitor ,monocyte-derived macrophage ,Microglia ,Gene Expression Profiling ,Macrophages ,Monocyte ,Cell Biology ,Dendritic cell ,Phenotype ,030104 developmental biology ,medicine.anatomical_structure ,monocyte ,Single-Cell Analysis ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Summary 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., Graphical abstract, Highlights • A reference transcriptome atlas for human macrophage biology • Culture alters primary myeloid phenotypes • Pluripotent stem cell–derived macrophages retain a common stromal signature • FLT3L-derived cord blood DCs lack expression of key pattern recognition receptors, In this article, Wells and colleagues describe an integrated myeloid transcriptome atlas. Analysis resulted in tissue-resident populations being categorized into three broad classes, with culture also found to impact primary cell phenotypes. Pluripotent stem cell–derived cells were compared with their in vivo counterparts, differing in maturation, efferocytosis capacity, and ectopic expression of extracellular matrix genes.
- Published
- 2021