Two Proteins Found To Maintain Self-Renewal In Embryonic Stem Cells.

MELBOURNE, Australia, April 17, 2019 -- An international research collaboration has discovered that two epigenetic regulators, TAF5L and TAF6L, maintain self-renewal of embryonic stem cells.

The proteins activate c-Myc (a well-known cancer gene), and its regulatory network.

This is the first time scientists have been able to show what these regulators do and how they control gene expression.

Embryonic stem cells (ESC) have the ability to self-renew and, being pluripotent, have the potential to create almost any cell type in the body.

The embryonic stem cell state is established and maintained by multiple regulatory networks that include epigenetic regulators; the function of these epigenetic regulators though has not been well-defined.

The collaboration was led by Monash Biomedicine Discovery Institute (BDI) scientists.

Monash BDI's Partha Pratim Das said TAF5L and TAF6L were discovered in a CRISPR-Cas9 loss-of -function genetic screen aimed at finding epigenetic regulators from among 323 epigenetic genes and at establishing how these controlled the embryonic stem cell state.

"It has been known that these factors existed, but for the first time we showed what they do and how they control gene expression," Das said. "Their function was not known before. From our study we can show the exact mechanism and how these epigenetic regulators control gene expression."

The two main things found were that TAF5L and TAF6L transcriptionally activate the oncogene c-Myc, and also regulate OCT4 that is the master regulator of the embryonic stem cells.

The MYC regulatory network is predominantly controlled by them by which they maintain the self-renewal aspect of the embryonic stem cell state.

The findings would potentially make TAF5L and TAF6L very significant not only in the regenerative biology field but also in cancer research.

Das said TAF5L and TAF6L also play a crucial role in induced pluripotent stem cells (iPSCs), a type of pluripotent stem cell that can be generated from adult somatic cells.

The scientists are further investigating whether TAF5L and TAF6L are linked to various types of cancer and whether they play an important role in neurodevelopment, testing this in mouse and human brain organoids.

Citation: Davide Seruggia et al., TAF5L and TAF6L Maintain Self-Renewal of Embryonic Stem Cells via the MYC Regulatory Network. Molecular Cell, 2019; DOI: 10.1016/j.molcel.2019.03.025

Abstract/Article: http://bit.ly/2ZiKPps

Contact: Partha Pratim Das, partha.das@monash.edu