Elsevier

Differentiation

Volume 92, Issue 3, September 2016, Pages 66-83
Differentiation

Review article
Genetic tools for identifying and manipulating fibroblasts in the mouse

https://doi.org/10.1016/j.diff.2016.05.009Get rights and content

Abstract

The use of mouse genetic tools to track and manipulate fibroblasts has provided invaluable in vivo information regarding the activities of these cells. Recently, many new mouse strains have been described for the specific purpose of studying fibroblast behavior. Colorimetric reporter mice and lines expressing Cre are available for the study of fibroblasts in the organs prone to fibrosis, including heart, kidney, liver, lung, and skeletal muscle. In this review we summarize the current state of the models that have been used to define tissue resident fibroblast populations. While these complex genetic reagents provide unique insights into the process of fibrosis, they also require a thorough understanding of the caveats and limitations. Here, we discuss the specificity and efficiency of the available genetic models and briefly describe how they have been used to document the mechanisms of fibrosis.

Section snippets

Fibrosis

Fibrosis, the deposition of extracellular matrix in response to injury, inflammation, and aging, can be either reparative or reactive. The organs that commonly exhibit fibrosis include the heart, kidney, liver, and lung (Zeisberg and Kalluri, 2013, Rockey et al., 2015). Despite the fact that a chronic fibrogenic response ultimately leads to organ dysfunction and failure, accounting for an estimated one third of natural deaths worldwide (Zeisberg and Kalluri, 2013), few therapeutic options have

Fibroblast definition

One of the key issues to understanding fibrosis is delineation of the role of the fibroblast. This endeavor is complicated, as the fibroblast is poorly defined and sometimes considered immature in regards to its differentiation status (Alberts et al., 2002). Anatomically, a fibroblast is described as a connective tissue cell that produces extracellular matrix (Alberts et al., 2002). Within this definition there are two main classifications: the adventitial fibroblast that surrounds blood

Cardiac fibroblasts

Similar to fibroblasts in other organs, cardiac fibroblasts are a poorly-defined cell population (Snider et al., 2009). Commonly, vimentin, collagen production, CD90, and DDR2 expression have been used to define the quiescent cardiac fibroblast population, while αSMA expression defines the activated fibroblast (Travers et al., 2016). Because many of these markers are expressed by other cell types, it has been difficult to generate a genetic tagging system that is specific to cardiac

Concluding remarks

It is clear from existing data that tools for effectively identifying and manipulating tissue resident cells with fibrogenic potential are in their infancy. The lack of a consensus regarding phenotypic markers for these cells under non-pathological conditions stems from the fact that clear designations for these cell types have not been determined. Recent data has refined our ideas relating to the cell types involved and have reinforced the notion that fibrogenic cells in each organ have unique

Funding sources

This work was supported by National Heart, Lung, and Blood Institute grants [HL074257, HL100401 to M.D.T.]; [F31HL126512 to M.J.I]; [F31HL128048 to J.M.S.]; and an Institutional Cardiology Training Grant position [T32 HL115505 to J.M.S.].

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