Fate Tracing Reveals the Pericyte and Not Epithelial Origin of Myofibroblasts in Kidney Fibrosis

Humphreys, Benjamin D.; Lin, Shuei Liong; Kobayashi, Akio; Hudson, Thomas E.; Nowlin, Brian T.; Bonventre, Joseph V.; Valerius, M. Todd; McMahon, Andrew P.; Duffield, Jeremy S.

doi:10.2353/ajpath.2010.090517

Cited by 1,262 publications

(1,288 citation statements)

References 62 publications

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“…PDGFRβ/PDGF-BB is the main signalling pathway mediating pericyte recruitment during vessel development (Hellstrom et al, 1999). This same pathway has been reported in the recruitment of pericytes to injured tissue, where they eventually contribute to fibrosis in organs such as the lung (Hung et al, 2013) and kidney (Humphreys et al, 2010;Lin et al, 2011;Schrimpf et al, 2012). Activated pericytes have been shown to detach from local capillaries, migrate to the site of injury and differentiate into myofibroblasts (Goritz et al, 2011;Lin et al, 2011;Ren et al, 2013).…”

Section: Mechanisms Of Msc and Pericyte Recruitment To Sites Of Injurysupporting

confidence: 60%

“…The authors go on to show that the differentiation of pericytes into myofibroblasts is driven by SnaiI and Id1 transcripts (Lin et al, 2008). Further studies employing fate mapping in mouse models of UUO have established that pericytes, not ECs, undergo proliferative expansion and differentiate into myofibroblasts during UUO (Humphreys et al, 2010). Further analysis into Type 1 and 2 subpopulations of pericytes show that pericytes react differently to injury depending on the organ affected.…”

Section: Tissue Fibrosismentioning

confidence: 99%

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Pericytes, mesenchymal stem cells and their contributions to tissue repair

Wong

Rowley

Redpath

et al. 2015

Pharmacology & Therapeutics

142

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Regenerative medicine using mesenchymal stem cells for the purposes of tissue repair has garnered considerable public attention due to the potential of returning tissues and organs to a normal, healthy state after injury or damage has occurred. To achieve this, progenitor cells such as pericytes and bone marrow-derived mesenchymal stem cells can be delivered exogenously, mobilised and recruited from within the body or transplanted in the form organs and tissues grown in the laboratory from stem cells. In this review, we summarise the recent evidence supporting the use of endogenously mobilised stem cell populations to enhance tissue repair along with the use of mesenchymal stem cells and pericytes in the development of engineered tissues. Finally, we conclude with an overview of currently available therapeutic options to manipulate endogenous stem cells to promote tissue repair.

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Section: Mechanisms Of Msc and Pericyte Recruitment To Sites Of Injurysupporting

confidence: 60%

Section: Tissue Fibrosismentioning

confidence: 99%

Pericytes, mesenchymal stem cells and their contributions to tissue repair

Wong

Rowley

Redpath

et al. 2015

Pharmacology & Therapeutics

142

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“…Lineage tracing of these FoxD1 progenitors, combined with a Col1 reporter system, identified four distinct mesenchymal populations in the healthy adult lung ( Figure 2 and Table 2): FoxD1 progenitor-derived Col1 À , FoxD1 progenitorderived Col1 þ , FoxD1-independent Col1 þ , and VSMC (referred to as FoxD1 þ /Col1 À , FoxD1 þ /Col1 þ , FoxD1 À / Col1 þ , and VSMC). 10,38 These mesenchymal cell types accounted for approximately 20% of all lung cells. FoxD1 expression was only detected between days 11 and 13 of embryogenesis in the lung buds, and the descendants of the transiently FoxD1-expressing population are crucial for the developing lung to mature.…”

Section: Mesenchymal Progenitors Traced From Developmentmentioning

confidence: 99%

Lung Pericytes and Resident Fibroblasts

Barron

Gharib

Duffield

2016

The American Journal of Pathology

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100

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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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“…A Six2-Tet-GFP-Cre allele is active exclusively within nephron progenitors; consequently, historical labeling results in EGFP-L10a expression throughout the main body of the nephron (24). A Foxd1-GFP-Cre allele is active in the progenitors of many of the interstitial cell lineages, including those generating mesangial and nonglomerular pericytes (25). In addition, Foxd1 is normally expressed in podocytes.…”

Section: Generation Of a Conditional Egfp-l10a Mouse Linementioning

confidence: 99%

Cell-specific translational profiling in acute kidney injury

et al. 2014

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Acute kidney injury (AKI) promotes an abrupt loss of kidney function that results in substantial morbidity and mortality. Considerable effort has gone toward identification of diagnostic biomarkers and analysis of AKI-associated molecular events; however, most studies have adopted organ-wide approaches and have not elucidated the interplay among different cell types involved in AKI pathophysiology. To better characterize AKI-associated molecular and cellular events, we developed a mouse line that enables the identification of translational profiles in specific cell types. This strategy relies on CRE recombinase-dependent activation of an EGFP-tagged L10a ribosomal protein subunit, which allows translating ribosome affinity purification (TRAP) of mRNA populations in CRE-expressing cells. Combining this mouse line with cell type-specific CRE-driver lines, we identified distinct cellular responses in an ischemia reperfusion injury (IRI) model of AKI. Twenty-four hours following IRI, distinct translational signatures were identified in the nephron, kidney interstitial cell populations, vascular endothelium, and macrophages/monocytes. Furthermore, TRAP captured known IRI-associated markers, validating this approach. Biological function annotation, canonical pathway analysis, and in situ analysis of identified response genes provided insight into cell-specific injury signatures. Our study provides a deep, cell-based view of early injury-associated molecular events in AKI and documents a versatile, genetic tool to monitor cell-specific and temporal-specific biological processes in disease modeling.

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Fate Tracing Reveals the Pericyte and Not Epithelial Origin of Myofibroblasts in Kidney Fibrosis

Cited by 1,262 publications

References 62 publications

Pericytes, mesenchymal stem cells and their contributions to tissue repair

Pericytes, mesenchymal stem cells and their contributions to tissue repair

Lung Pericytes and Resident Fibroblasts

Cell-specific translational profiling in acute kidney injury

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