ABCG2<sup>pos</sup> lung mesenchymal stem cells are a novel pericyte subpopulation that contributes to fibrotic remodeling

Marriott, Shennea; Baskir, Rubin; Gaskill, Christa; Menon, Swapna; Carrier, Erica J.; Williams, Janice A.; Talati, Megha; Helm, Karen M.; Alford, Catherine E.; Kropski, Jonathan A.; Loyd, James E.; Wheeler, Lisa; Johnson, Joyce E.; Austin, Eric D.; Nozik‐Grayck, Eva; Meyrick, Barbara; West, James; Klemm, Dwight J.; Majka, Susan M.

doi:10.1152/ajpcell.00114.2014

Cited by 83 publications

(120 citation statements)

References 103 publications

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“…3,17,20,36,41 In support of this prospect, bleomycin lung injury reduces the number of ABCG2 þ MSCs, transferring exogenous MSCs ameliorates fibrosis, disabling the antioxidative functions of MSCs increases vulnerability to hypoxic stress, and fewer ABCG2 þ cells were detected in IPF than control samples from human donors. 17,36,41 However, MSCs also generate myofibroblasts and, although not tested in the lung, depletion of Gli1 þ MSCs reduces kidney and heart fibrosis. 20 Therefore, delivering or expanding MSCs may not be beneficial, or even detrimental, unless the signals stimulating their differentiation into myofibroblasts are first inhibited.…”

Section: Pericytes and Interstitial Fibroblasts In Lung Regenerationmentioning

confidence: 92%

“…3,5,17,20,36,41 ABCG2-expressing, or lineagemarked, NG2 À MSCs express mostly the same genes at similar levels as NG2 þ cells, but lower levels of Table 2). Dashed lines indicate additional hypotheses for the origins of a-smooth muscle actin (a-SMA) À pathogenic fibroblasts in injured lung.…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 96%

“…36 Nonetheless, ABCG2-marked cells either directly or indirectly differentiated into myofibroblasts at fibrotic foci after lung injury. 17 Whether these MSCs are the same as Gli1 þ MSCs remains to be established.…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

“…2,9,10,13 Pericytes and resident lung fibroblasts can be identified independently of their location, with appropriate criteria for excluding other cell types, by their expression of markers, including PDGF receptor (PDGFR) b and a, CD146, NG2, a-SMA, collagen I(a)1 (Col1), vimentin, and desmin (Table 1). 2,3,9,10,17 However, the fidelity of these markers varies by context. They differ between species and organs; can be present on other cell types; are altered by stage of organ development, activation signals, or injury; and can undergo either rapid or gradual change during cell culture.…”

Section: Characteristics Of Lung Pericytes and Resident Fibroblastsmentioning

confidence: 99%

“…10 Perivascular Gli1 þ or ABCG2 þ MSCs also differentiate into myofibroblasts, although they might transition to become pericytes first. 17,20,41 Caveats apply to these data. Lineage tracing systems are limited by specificity, efficiency, and sensitivity.…”

Section: Myofibroblasts In Lung Fibrosis and Degenerationmentioning

confidence: 99%

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Lung Pericytes and Resident Fibroblasts

Barron

Gharib

Duffield

2016

The American Journal of Pathology

109

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Pericytes, resident fibroblasts, and mesenchymal stem cells are poorly described cell populations. They have recently been characterized in much greater detail in rodent lungs and have been shown to play important roles in development, homeostasis, response to injury and pathogens, as well as recovery from damage. These closely related mesenchymal cell populations form extensive connections to the lung's internal structure, as well as its internal and external surfaces. They generate and remodel extracellular matrix, coregulate the vasculature, help maintain and restore the epithelium, and act as sentries for the immune system. In this review, we revisit these functions in light of significant advances in characterizing and tracking lung fibroblast populations in rodents. Lineage tracing experiments have mapped the heritage, identified functions that discriminate lung pericytes from resident fibroblasts, identified a subset of mesenchymal stem cells, and shown these populations to be the predominant progenitors of pathological fibroblasts and myofibroblasts in lung diseases. These findings point to the importance of resident lung mesenchymal populations as therapeutic targets in acute lung injury as well as fibrotic and degenerative diseases. Far from being passive and quiescent, pericytes and resident fibroblasts are busily sensing and responding, through diverse mechanisms, to changes in lung health and function. (Am J Pathol 2016 http://dx

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Section: Pericytes and Interstitial Fibroblasts In Lung Regenerationmentioning

confidence: 92%

Section: Mesenchymal Stem Cellsmentioning

confidence: 96%

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

Section: Characteristics Of Lung Pericytes and Resident Fibroblastsmentioning

confidence: 99%

Section: Myofibroblasts In Lung Fibrosis and Degenerationmentioning

confidence: 99%

See 3 more Smart Citations

Lung Pericytes and Resident Fibroblasts

Barron

Gharib

Duffield

2016

The American Journal of Pathology

109

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Genotoxicity and Carcinogenic Potential of Carbon Nanomaterials

Stueckle

Sargent

Rojanasakul

et al. 2016

Biomedical Applications and Toxicology of Carbon Nanomaterials

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Pathogenic Activation of Mesenchymal Stem Cells Is Induced by the Disease Microenvironment in Systemic Sclerosis

Taki

Gostjeva

Thilly

et al. 2020

Arthritis & Rheumatology

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Objective In systemic sclerosis (SSc) a persistent tissue repair process leads to progressive fibrosis of the skin and internal organs. The role of mesenchymal stem cells (MSCs), which characteristically initiate and regulate tissue repair, has not been fully evaluated. We sought to investigate whether dividing metakaryotic MSCs are present in SSc skin, and test whether exposure to the disease microenvironment activates MSCs leading to transdifferentation. MethodsSkin biopsy material from recent onset diffuse SSc patients was examined by collagenase spread of 1mm thick surface-parallel sections, in order to identify metakarytoic dividing stem cells in each tissue plane. Adipose-derived MSCs from healthy controls were treated with dermal blister fluid from diffuse SSc patients, and profiled by next generation sequencing, or evaluated for phenotypic changes relevant to SSc. Differential responses of dermal fibroblasts were studied in parallel. Results MSC-like cells undergoing active metakaryotic division were identified in SSc but not control sections, most prominent in the deep dermis and adjacent to damaged microvessels, in both involved and clinically uninvolved skin. Furthermore, exposure to SSc blister fluid caused selective MSC activation, inducing a myofibroblast signature, whilst reducing signatures of vascular repair and adipogenesis and enhancing migration and contractility. Microenvironment factors implicated in inducing transdifferentiation include the pro-fibrotic growth factor TGFβ, presence of lactate and mechanosensing, whereas the microenvironment Th2 cytokine IL-31, enhanced osteogenic commitment (calcinosis). Conclusion Dividing MSC-like cells are present in the SSc disease microenvironment where multiple factors, likely acting in concert, promote transdifferentiation, leading to a complex and resistant disease state.

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ABCG2^pos lung mesenchymal stem cells are a novel pericyte subpopulation that contributes to fibrotic remodeling

Abstract: DJ, Majka SM. ABCG2 pos lung mesenchymal stem cells are a novel pericyte subpopulation that contributes to fibrotic remodeling.

Cited by 83 publications

References 103 publications

Lung Pericytes and Resident Fibroblasts

Lung Pericytes and Resident Fibroblasts

Genotoxicity and Carcinogenic Potential of Carbon Nanomaterials

Pathogenic Activation of Mesenchymal Stem Cells Is Induced by the Disease Microenvironment in Systemic Sclerosis

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ABCG2pos lung mesenchymal stem cells are a novel pericyte subpopulation that contributes to fibrotic remodeling

Abstract: DJ, Majka SM. ABCG2 pos lung mesenchymal stem cells are a novel pericyte subpopulation that contributes to fibrotic remodeling.

Cited by 83 publications

References 103 publications

Lung Pericytes and Resident Fibroblasts

Lung Pericytes and Resident Fibroblasts

Genotoxicity and Carcinogenic Potential of Carbon Nanomaterials

Pathogenic Activation of Mesenchymal Stem Cells Is Induced by the Disease Microenvironment in Systemic Sclerosis

Contact Info

Product

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About

ABCG2^pos lung mesenchymal stem cells are a novel pericyte subpopulation that contributes to fibrotic remodeling