HEXIM1 regulatory protein induces human pluripotent stem cells to adopt more specialized cell fate

December 19, 2013, Agency for Science, Technology and Research (A*STAR), Singapore
Stem cells: A HEX that coaxes differentiation
Human pluripotent stem cells, such as human embryonic stem cells (above), can differentiate into specific cell types under appropriate conditions; the HEXIM1 protein helps with this differentiation. Credit: DAJ/amana images/Thinkstock

A lot of optimism and promise surrounds the use of human pluripotent stem cells (hPSCs) for applications in regenerative medicine and drug discovery. However, technical challenges still hamper the culturing and differentiation of these cells, which include the cell types known as human embryonic stem cells (hESCs) and their reprogrammed equivalents, induced pluripotent stem cells (iPSCs).

A team of A*STAR scientists has now discovered a regulatory protein that helps to coax human to form more specialized types of cells. "Our finding could help to develop a new protocol to induce of human pluripotent stem cells," says Sheng-Hao Chao from the A*STAR Bioprocessing Technology Institute (BTI) in Singapore, who led the study.

Chao and his co-workers at the BTI's Expression Engineering Group have been studying a protein called hexamethylene bisacetamide-inducible protein 1 (HEXIM1) for many years. HEXIM1 is known to inhibit a protein complex called positive transcription elongation factor b (P-TEFb), which is involved in gene expression. Chao's team previously linked HEXIM1 with a specific pathway involved in cancer development. This led the researchers to suspect an additional role for HEXIM1 in regulating stem cells.

Chao's group teamed up with Andre Choo and his colleagues in the Stem Cell Group at the BTI to further explore this possibility. They first treated hESCs with a differentiation-inducing compound called LY294002 and saw a marked increase in HEXIM1 levels compared to untreated cells.

Further tests showed that HEXIM1 played a role in driving cellular differentiation. For example, the hESCs differentiated when the researchers incubated the cells with hexamethylene bisacetamide (HMBA), a HEXIM1 inducing reagent, or when they generated and cultured a cell line with elevated expression of HEXIM1. The researchers rule out P-TEFb inhibition as an explanation for the effect, however, because in another experiment, hESCs treated with flavopiridol—a drug that blocks P-TEFb activity—remained in a pluripotent state.

"We discovered a novel function of HEXIM1 in regulating the early-stage differentiation of human pluripotent stem cells through a P-TEFb-independent pathway," says Chao. More work is still needed to investigate in detail the molecular mechanism by which HEXIM1 drives hPSC differentiation.

Eventually, HEXIM1 could become a useful tool in generating new tissues for cell-replacement therapies. "In combination with other transcription factors or chemicals, it is possible that HEXIM1 and its inducing reagent HMBA could be utilized to direct the differentiation of pluripotent  into specific ," Chao says.

Explore further: Putting a 'HEX' on muscle regeneration

More information: Ding, V., Lew, Q. J., Chu, K. L., Natarajan, S., Rajasegaran, V. et al. "HEXIM1 induces differentiation of human pluripotent stem cells." PLoS ONE 8, e72823 (2013). dx.doi.org/10.1371/journal.pone.0072823

Lew, Q. J., Chia, Y. L., Chu, K. L., Lam, Y. T., Gurumurthy, M. et al. "Identification of HEXIM1 as a positive regulator of p53." Journal of Biological Chemistry 287, 36443–36454 (2012). dx.doi.org/10.1074/jbc.M112.374157

Related Stories

Putting a 'HEX' on muscle regeneration

October 1, 2012

A complex genetic regulatory network mediates the regeneration of adult skeletal muscles. In this issue of the Journal of Clinical Investigation, researchers at the State University of New York Downstate Medical Center in ...

Scientists engineer human stem cells

December 6, 2013

In an important scientific breakthrough in regenerative medicine, researchers at A*STAR's Genome Institute of Singapore have successfully converted human embryonic stem cells (hESCs) cultured in the laboratory to a state ...

A step closer to muscle regeneration

December 10, 2013

(Medical Xpress)—Muscle cell therapy to treat some degenerative diseases, including Muscular Dystrophy, could be a more realistic clinical possibility, now that scientists have found a way to isolate muscle cells from embryonic ...

Scientists isolate new human pluripotent stem cells

October 31, 2013

One of the obstacles to employing human embryonic stem cells for medical use lies in their very promise: They are born to rapidly differentiate into other cell types. Until now, scientists have not been able to efficiently ...

Recommended for you

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

not rated yet Dec 21, 2013
New Book on Stem Cell Transplants.

TRANSPLANT HANDBOOK FOR PATIENTS: Replacing #Stem Cells in Your Bone #Marrow.
By a 75-year old author, in Day +138 since his transplant, who is setting records for recovery.
This book helps the #cancer patient, caregiver, and family to understand the #stem cell #transplant journey.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.