Thursday, 24 October 2013

USC researchers reveal novel methods to better master the fate of stem cells

USC researcher Qi-Long Ying has found
a new way of culturing human embryonic
stem cells.
(Image courtesy of Qi-Long Ying)
USC scientist Qi-Long Ying and his team have long been searching for biotech's version of the fountain of youth. And that is new ways to encourage embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) to endlessly self-renew, or divide to produce more stem cells.

In a series of studies published in Nature Communications in September and inThe EMBO Journal in August, Ying and his colleagues revealed some of the ways that ESCs and EpiSCs use to retain their pluripotency, in other words their ability to differentiate into virtually any type of cell.

In the Nature Communications study they discovered a novel way of culturing human ESCs by focusing on the Wnt/beta-catenin signaling pathway -- a group of molecules that work together to control various cell functions, including some related to embryonic development.

The researchers say that this pathway can prompt mouse EpiSCs and human ESCs to either self-renew or differentiate. When the protein beta-catenin remains within the cell cytoplasm but outside of the nucleus, the stem cell continues to self-renew. When beta-catenin moves into a stem cell's nucleus, differentiation begins.

The paper published in The EMBO Journal addresses mouse ESCs, which are derived from the embryo at an earlier stage and are more pluripotent than mouse EpiSCs.

lllustration provided by Qing Liu-Michael

The study revealed the important role of Tfcp2l1, a transcription factor, or protein that controls which genes are turned on and off in a cell.

In mice, Tfcp2l1 helps communicate to ESCs that they should self-renew. The transcription factor also shows promise for "rewinding" slightly more differentiated EpiSCs into the more naïve ESC state.

Illustration provided by Qing Liu-Michael

By learning more about the ESC and EpiSC playbooks, Ying and his colleagues can better control stem cell self-renewal, offering hope for patients with currently untreatable diseases and creating potential for a wide variety of other applications.

"These new findings have allowed us to develop conditions for the efficient propagation of human ESCs, and might also enable us to establish pluripotent stem cells from different species. This has far-reaching implications for a variety of applied areas of investigation, ranging from manipulating the genomes of agricultural animals to developing stem cell-based therapies for ailments such as Parkinson's disease or spinal cord injuries." said Ying, associate professor of stem cell biology and regenerative medicine at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC. 

1) Kim H, Wu J, Ye S, Tai CI, Zhou X, Yan H, Li P, Pera M, & Ying QL (2013). Modulation of β-catenin function maintains mouse epiblast stem cell and human embryonic stem cell self-renewal. Nature communications, 4 PMID: 23985566
2) Ye S, Li P, Tong C, & Ying QL (2013). Embryonic stem cell self-renewal pathways converge on the transcription factor Tfcp2l1. The EMBO journal, 32 (19), 2548-60 PMID: 23942238

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