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. 2008 Aug 7;3(2):132-5.
doi: 10.1016/j.stem.2008.06.019.

Wnt signaling promotes reprogramming of somatic cells to pluripotency

Alexander Marson, Ruth Foreman, Brett Chevalier, Steve Bilodeau, Michael Kahn, Richard A Young, Rudolf Jaenisch

Wnt signaling promotes reprogramming of somatic cells to pluripotency

Alexander Marson et al. Cell Stem Cell. .
No abstract available

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Figures

Figure 1
Figure 1. Wnt3a promotes reprogramming of somatic cells to pluripotency
a. Scatter plots comparing GFP intensity to autofluoresence, using flow cytometry, in Oct4-GFP cells on day 20 post-induction of Oct4/Sox2/Klf4, reveal a GFP expressing population of cells (indicated with an arrow) only with Wnt3a-CM treatment (right), not in the control (Ctrl) Oct4/Sox2/Klf4-infected cells cultured in standard ES cell medium (left). b. Phase-contrast micrographs (Phase, left) of GFP expressing Myc[-] cells derived with Wnt3a-CM treatment and without any genetic selection. Immunostaining reveals induction of pluripotency markers, Nanog (upper) and SSEA-1(lower) in Wnt3a-CM treated Myc[-] cells. c. Wnt3a-CM treated Myc[-] lines formed teratomas when injected into SCID mice subcutaneously. Teratomas from Oct4/Sox2/Klf4/Wnt3a-CM iPS lines showed evidence of differentiated cells of three germ layers similar to teratomas formed from V6.5 mES injections. Arrows indicated neural tissue in (upper), cartilage in (middle), and endodermal cells in (lower), d. Oct4/Sox2/Klf4/Wnt3aCM iPS lines derived without selection gave rise to chimeric mice (as shown on the left) with agouti coat color and pigmented eyes (in contrast to wild type Balb/c mouse, right) providing evidence of contribution to somatic cells. e. Agouti coat color of offspring (left) of chimeric mouse (right) confirmed that the Oct4/Sox2/Klf4/Wnt3a-CM iPS line generated here is germline-competent.
Figure 2
Figure 2. Wnt/ß-catenin stimulation enahances iPS colony formation in absence of c-Myc retrovirus
a. Counts are shown for G418-resistant colonies in Oct4/Sox2/Klf4 over-expressing MEFs cultured in ES cell media, control L cell conditioned media (ATCC), Wnt3a over-expressing conditioned media (ATCC), and Wnt3a over-expressing conditioned media with ICG-001 (4μM). Selection was initiated on day 15 post-induction, and colonies were assessed on day 28. Wnt3a-CM treatment was maintained for 6-9 days after selection was initiated. Mean number of counts from triplicate experiments is displayed with error bars indicating S.D. b. Counts are shown for G418-resistant colonies (in a 32cm2 area) in Oct4/Sox2/Klf4/c-Myc over-expressing MEFs cultured in ES cell media, Wnt3a over-expressing conditioned media (ATCC), and Wnt3a over-expressing conditioned media with ICG-001 (4μM). Selection was initiated on day 10 post-induction, Wnt3a-CM was maintained for the first 6-9 days of selection, and colonies were assessed on day 20. c. Wnt stimulation promotes the formaton of iPS cells in the absence of c-Myc transduction. This could be due to: i) direct regulation by the Wnt pathway of key endogenous pluripotency factors, such as Oct4, Sox2 and Nanog as suggested by genomic studies in ES cells (Cole et al., 2008), ii) Wnt pathway-induced activation of endogenous Myc (He et al., 1998; Cole et al., 2008), or other cell proliferation genes, accelerating the sequential process of forming iPS colonies.
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References

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