Stem Cells and Wnt Signaling
Stem cells are defined as having the capacity to self-renew while also producing specialized cells. Thereby, stem cells retain their developmental potential over the long term. Lineage tracing based on Wnt target genes such as Lgr5 and Axin2 have provided evidence for Wnts as critical stem cell signals. Wnt-target gene labeled stem cells have been detected in organs ranging from the intestine to the stomach, the skin, the hair follicle, and the mammary gland (see table below and figure, right). These choices of stem cells to self-renew or to differentiate are dictated by extrinsic signals with a short range of action, thereby limiting the number of stem cells in tissues. The signals and the cells that produce them are known as the niche. Wnt signals, lipid modified and therefore restricted in their range of action, are widely implicated as niche factors (reviewed by Clevers, Loh, Nusse 2014, PDF).
The mechanism by which Wnt signals maintain stem cells may include a block in differentiation, possibly by suppressing differentiation-specific genes. Differentiation is thought to be the default step of a dividing stem cell.
The implications of the connection between Wnt and stem cells include the use of Wnt proteins or Wnt agonists to maintain stem cells in culture. While stem cells are difficult to expand in a self-renewing state, adding Wnts or R-Spondins has overcome some of these problems (Zeng 2010, Sato 2009).
A clone of Axin2-labeled cells in mouse skin tissue (from Lim 2013)
|Tissue||Stem Cell||Marked by||References|
|Intestine||Crypt base columnar cell||Lgr5||Barker 2007|
|Mammary gland||Basal cell||Axin2, Lgr5, Procr||Van Amerongen 2012, De Visser 2012, Wang 2015, Plaks 2013|
|Stomach||Basal pyloric cell||Lgr5||Barker 2010|
|Interfollicular epidermis||Basal cell||Axin2||Lim 2013|
|Central nervous system||Radial glial cell||Axin2||Bowman 2013|
|Hair follicle||Outer bulge cell||Lgr5, Axin2||Jaks 2008, Lim et al 2016|
|Kidney||Nephron segment-specific stem cell||Lgr5, Axin2||Barker 2012, Rinkevich 2014|
|Cochlea||Tympanic border cell||Axin2, Lgr5||Jan 2013, Shi 2013|
|Ovary||Hilum ovarian surface epithelial cell||Lgr5||Flesken-Nikitin 2013, Ng 2014|
|Taste bud||Circumvallate papilla stem cell||Lgr5||Yee 2013|
|Liver||Pericentral hepatocyte||Axin2||Wang 2015|
|Embryonic stem||Embryonic stem||Axin2||Ten Berge 2011|
|Testis||Spermatogonial stem cell||Axin2||Takase et al, 2016|