Nav: Home

Study reveals factors behind embryonic stem cell state

April 17, 2019

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.

An international collaboration led by Monash Biomedicine Discovery Institute (BDI) scientists has found for the first time that two new epigenetic regulators, TAF5L and TAF6L, maintain self-renewal of embryonic stem cells. The scientists also found that these proteins activate c-Myc (a well-known cancer gene), and its regulatory network.

Their findings were published in Molecular Cell today.

Monash BDI's Dr 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," Dr Das said. "Their function was not known before," he said.

"From our study we can show the exact mechanism and how these epigenetic regulators control gene expression."

"The two main things we 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."

"We found that 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, he said.

Dr 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.

Instrumental in the study were Professor Stuart Orkin (Howard Hughes Medical Institute) and Dr Davide Seruggia (Dana Farber Cancer Institute and Boston Children's Hospital, Harvard Medical School), and the Monash BDI's Dr Pratibha Tripathi, Dr Martin Oti and Michael Bullen.

This research was supported by the National Health and Medical Research Council of Australia (NHMRC).

Read the full paper in Molecular Cell titled TAF5L and TAF6L maintain self-renewal of embryonic stem cells via the MYC regulatory network.
-end-
About the Monash Biomedicine Discovery Institute

Committed to making the discoveries that will relieve the future burden of disease, the newly established Monash Biomedicine Discovery Institute at Monash University brings together more than 120 internationally-renowned research teams. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.

Monash University

Related Cancer Articles:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Cancer expert says public health and prevention measures are key to defeating cancer
Is investment in research to develop new treatments the best approach to controlling cancer?
UI Cancer Center, Governors State to address cancer disparities in south suburbs
The University of Illinois Cancer Center and Governors State University have received a joint four-year, $1.5 million grant from the National Cancer Institute to help both institutions conduct community-based research to reduce cancer-related health disparities in Chicago's south suburbs.
Leading cancer research organizations to host international cancer immunotherapy conference
The Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research will join forces to sponsor the first International Cancer Immunotherapy Conference at the Sheraton New York Times Square Hotel in New York, Sept.

Related Cancer Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Changing The World
What does it take to change the world for the better? This hour, TED speakers explore ideas on activism—what motivates it, why it matters, and how each of us can make a difference. Guests include civil rights activist Ruby Sales, labor leader and civil rights activist Dolores Huerta, author Jeremy Heimans, "craftivist" Sarah Corbett, and designer and futurist Angela Oguntala.
Now Playing: Science for the People

#521 The Curious Life of Krill
Krill may be one of the most abundant forms of life on our planet... but it turns out we don't know that much about them. For a create that underpins a massive ocean ecosystem and lives in our oceans in massive numbers, they're surprisingly difficult to study. We sit down and shine some light on these underappreciated crustaceans with Stephen Nicol, Adjunct Professor at the University of Tasmania, Scientific Advisor to the Association of Responsible Krill Harvesting Companies, and author of the book "The Curious Life of Krill: A Conservation Story from the Bottom of the World".