1. Mesenchymal Stem Cells in Fibrotic Disease
Elie El Agha, Rafael Kramann, Rebekka K. Schneider, Xiaokun Li, Werner Seeger, Benjamin D. Humphreys, Saverio Bellusci 
Cell Stem Cell 
Volume 21, Issue 2, Pages (August 2017)
DOI: /j.stem
Copyright © 2017 Elsevier Inc. Terms and Conditions

2. Figure 1
Resident Perivascular GLI1+ Cells Are a Major Source of Myofibroblasts in Kidney Fibrosis
Injury leads to dedifferentiation of tubular epithelial cells (partial EMT). The dedifferentiated tubular epithelial cells secrete multiple factors that activate perivascular GLI1+ MSC-like cells around capillaries and arteries/arterioles, leading to their detachment and differentiation into ECM-secreting myofibroblasts. Detachment of GLI1+ cells from capillaries leads to capillary destabilization and loss, with subsequent hypoxia leading to further tubular injury and fibrosis. Resident fibroblasts are also believed to contribute to the myofibroblast pool, while the contribution of bone-marrow-derived cells, such as fibrocytes and macrophages, to kidney fibrosis remains controversial.
Cell Stem Cell  , DOI: ( /j.stem )
Copyright © 2017 Elsevier Inc. Terms and Conditions

3. Figure 2
Cellular Origins of Myofibroblasts in Idiopathic Pulmonary Fibrosis
Activated myofibroblasts in lung fibrosis are believed to originate from resident fibroblasts (presumably TBX4+) and pericytes undergoing activation, alveolar epithelial cells (AECs) undergoing epithelial-to-mesenchymal transition (EMT), and circulating fibrocytes that are recruited from the bone marrow. Resident perivascular MSC-like cells (GLI1+ and ABCG2+ cells) have also been shown to undergo proliferation and differentiation into myofibroblasts. More recently, resident lipofibroblasts undergoing phenotypic switching have also been identified as a potential source of fibrosis-associated myofibroblasts. During the resolution phase of bleomycin-induced pulmonary fibrosis, a subpopulation of myofibroblasts reverts to a lipofibroblast-like phenotype.
Cell Stem Cell  , DOI: ( /j.stem )
Copyright © 2017 Elsevier Inc. Terms and Conditions

4. Figure 3
Model for the Involvement of Resident MSC-like Cells in Organ Fibrosis
Under the influence of pro-inflammatory and pro-fibrotic cytokines in addition to other genetic and unknown factors, organ-resident MSC-like cells undergo direct transdifferentiation into myofibroblasts. Paracrine-acting factors derived from MSC-like cells may also trigger activation and transdifferentiation of other mesenchymal cells into myofibroblasts. Red lines indicate direct transdifferentiation of mesenchymal cells and MSC-like cells into myofibroblasts during fibrosis development. Green lines indicate dedifferentiation of myofibroblasts into more benign mesenchymal cells during fibrosis resolution (for example, in the lung, heart, and skin). Genetic lineage tracing and single-cell RNA-seq should be used to study heterogeneity and transcriptomic signatures of not only myofibroblasts and their precursor cells but also their descendants (as indicated by dashed arrows) during fibrosis resolution.
Cell Stem Cell  , DOI: ( /j.stem )
Copyright © 2017 Elsevier Inc. Terms and Conditions