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

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 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.

Proliferation drives quorum sensing of microbial products in human macrophage populations

“…Through the construction of the Myeloid Atlas (Rajab et al 2021), we further observed that PSCMs shared the transcriptional phenotype of tissue-resident mфs.…”

“…Pluripotent stem cell-derived mϕs (PSCMs) are considered equivalent to tissue resident mϕs because these share ontogenic and transcriptional programs (Buchrieser et al 2017; Calvanese et al 2022) and are functionally equivalent to tissue resident mϕs in engraftment models in brain and lung (Takata et al 2017). Through the construction of the Myeloid Atlas (Rajab et al 2021), we further observed that PSCMs shared the transcriptional phenotype of tissue-resident mϕs. As PSCMs are representative of tissue-resident cells, they provide an experimental model to investigate sources of population heterogeneity in bacterial responses.…”

The Human Dendritic Cell Atlas: An integrated transcriptional tool to study human dendritic cell biology

“…Dataset integration and gene selection for PCA For the integration step, the common genes between all datasets were selected and assessed for their platform dependency as described in detail by (Angel et al, 2020) and (Rajab et al, 2021). Briefly, the gene expression values from RNA Sequencing and Microarray were transformed into percentile values.…”

“…Capybara (Kong et al 2020) identity scores were used to measure the similarity of the external pseudo-bulk samples to the reference atlas. Capybara cell scores were calculated by performing a restricted linear regression of atlas samples on each of the pseudo-bulk samples' expression profiles as described previously by (Rajab et al, 2021).…”

Human Monocytes Plasticity in Neurodegeneration

“…One way to address this issue is to study subset gene expression profiles. Microarray technology has been extensively applied to study monocytes to discover if specific gene expression profiles exist for each human subset [12][13][14]. Recently, a complete compendium of monocyte gene expression studies has been published by collecting 93 public datasets corresponding to 4516 transcriptomes.…”