Cross-tissue organization of the fibroblast lineage

Abstract

Data Fig. 3a-c, Supplementary Table 3). An interactive data browser for the atlases is publicly available (see 'Data availability'). Notably, our bulk RNA-seq and single-cell data were highly concordant, which indicates that our single-cell analytical approach did not introduce technical bias (Extended Data Fig. 3d).

The small and large intestine contain transcriptionally related mesenchymal stromal cell subsets that derive from embryonic Gli1+ mesothelial cells

“…While early trajectory analysis suggested a bifurcation downstream from CD81 + FB (Kinchen et al, 2018), our tSPACE, pseudotime and Velocity analyses suggested that adult colonic CD81 + FB connected in a linear direction to adult CD90 + FB, then to Fgfr2 + FB and finally to PDGFR hi FB. Although we used different markers, our findings are consistent with those recently published by Buechler et al who suggested that adventitial Pi16 + FB give rise first to Col151 + FB and then to tissue specific FB clusters that in the intestine included Fbln1 + FB and subsequently Bmp4 + FB (Buechler et al, 2021). Overlaying these clusters on our tSPACE trajectories demonstrated that the Pi16 + , Col151 + and Fbln1 + FB most closely resembled the CD81 + , CD90 + and Fgfr2 + FB we found in colon, while the Bmp4 + FB were similar to our colonic PDGFR hi FB.…”

“…5F). This conclusion was further supported when we overlaid our trajectory on to the DEG genes for clusters generated by a recent pseudotime analysis of mouse tissue FB, which has suggested a developmental trajectory from Pi16 + precursors through a population of Col151 + FB that eventually gives rise to mature tissue specific FB that include Fbln1 + and then Bmp4 + FB in the intestine (Buechler et al, 2021). This analysis showed that the Pi16 + , Col151 + , Fbln1 + and Bmp4 + FB clusters defined by Buechler et al broadly overlapped with our colonic CD81 + , CD90 + , Fgfr2 + and PDGFR hi FB subsets, respectively (Fig.…”

“…5E). As adventitial CD81 + FB have been suggested to contain FB precursors in adults (Buechler et al, 2021), we used them as the starting population for a new pseudotime analysis, which again indicated a linear trajectory from adult CD81 + FB via CD90 + FB and Fgfr2 + FB to PDGFR hi FB (Fig. 5F).…”

“…DEGs were identified using Seurat FindAllMarkers function with the default test setting (non-parameteric Wilcoxon Rank Sum test). Expression of gene modules in the form of published signature gene sets were calculated with AddModuleScore (Seurat) taking the top DEG from telocytes (10 genes), Lo-1 FB (10 genes) and Lo-2 FB (7 genes) reported by McCarthy et al (McCarthy et al, 2020), the top 10 DEG from FB1-5, MC and SMCs reported by Hong et al (Hong et al, 2020), and the top 20 DEG from Pi16 + , Col15a1 + , Fbln1 + and Bmp4 + FB reported by Buechler et al (Buechler et al, 2021). Pearson correlations between datasets were calculated based on average expressions per cluster of overlapping variable genes and plotted with heatmap.2 (version 3.0.3) (Gregory R. Warnes, Ben Bolker, Lodewijk Bonebakker, Robert Gentleman, Wolfgang Huber, Andy Liaw, Thomas Lumley, Martin Maechler, Arni Magnusson, Steffen Moeller and Venables, 2020).…”

Cellular Heterogeneity of Mesenchymal Stem/Stromal Cells in the Bone Marrow

“…In addition, single-cell atlases are available for tissues and organs, including adipose tissue ( Sun et al, 2020 ), heart ( Litvinukova et al, 2020 ), lungs ( Travaglini et al, 2020 ), lymph nodes ( Rodda et al, 2018 ), and hair follicles ( Gupta et al, 2019 ). The, single-cell technology has revealed a larger subset of cells and specific marker genes, which may help explain the regulatory networks underlying physiological and pathological conditions ( Buechler et al, 2021 ). These reports have improved our understanding of the identity of tissue-specific cell types and tissue diseases.…”