Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Induced Pluripotent Stem Cells Retain in Inactivate X Chromosome

06.09.2010
Female induced pluripotent stem (iPS) cells, reprogrammed from human skin cells into cells that have the embryonic-like potential to become any cell in the body, retain an inactive X chromosome, stem cell researchers at UCLA have found.

The finding could have implications for studying X chromosome-linked diseases such as Rett syndrome, caused by mutations in a gene located on the X chromosome.

The findings differ from those seen in mouse skin cells that are reprogrammed into iPS cells, in which the inactive X chromosome reactivates, said Kathrin Plath, senior author of the study and a scientist with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

“We knew from our studies that in reprogrammed mouse cells, the X chromosome becomes active again,” said Plath, an assistant professor of biological chemistry and one of the first scientists in the world to reprogram mouse and human adult cells into iPS cells. “The question we wanted to ask is what happens in female human iPS cells.”

All female cells have two X chromosomes – one from each parent - and in early development, one X chromosome is permanently inactivated. The inactivation of the X chromosome ensures that females, like males, have one functional copy of the X chromosome in each cell of the body and that the cells develop normally.

Plath and her team took human skin cells from females of varying ages. The cells have one active and one inactive X chromosome. The research team added four transcription factors to reprogram the cells into iPS cells and examined the resulting iPS cells to uncover the status of the X chromosome. They found that one X chromosome remained inactive, making the reprogrammed cells similar to most female human embryonic stem cells, which have one active and one inactive X chromosome. More than 30 different iPS cells lines were analyzed in the study, with the same result, Plath said.

‘The presence of the inactive X chromosome in the iPS cells raised the question of which of the two X chromosomes is inactive in the iPS cell lines,” Plath said.

During mouse and human embryonic development, one X chromosome is silenced in every female somatic cell, but the selection of either the paternal or maternal chromosome for silencing is random in each cell. A typical population of skin cells is mosaic for which X chromosome is silenced, containing about 50% of cells that inactivated the paternally inherited X, while the other 50% of cells inactivated the maternal X. Plath and her team sought to determine whether X chromosome silencing in iPS cell populations was random as well.

Plath found that all cells in the same reprogrammed iPS cell line exclusively expressed the same X chromosome and had the other X inactive. Also, Plath found that different iPS cells lines that came from the same adult skin cell population can differ in which X chromosome is inactivated.

Because the inactivated X is retained during human cell reprogramming and differentiation of iPS cells, these cells are well positioned for the study of X-linked diseases because it would be possible to get lines either expressing the normal or mutant allele from the same female patient.

“This non-random pattern of X chromosome inactivation found in iPS cell lines has critical implications for clinical applications and disease modeling and could be exploited for a unique form of gene therapy for X-linked diseases,” Plath said.

In collaboration with other stem cell researchers at UCLA, including Bill Lowry and April Pyle, they generated isogenic, or identical genetically, female iPS cell lines from females who are carriers of the mutation in the dystrophin gene on the X chromosome, making themcarriers for muscular dystrophy (DMD). They isolated iPS cell lines that either exclusively expressed the normal or the mutant version of the affected dystrophin gene responsible for DMD. These cells are isogenic and represent the perfect pair of control and mutant cell types for investigation of the disease phenotype. They currently are studying the effect of the mutation in muscle differentiation.

This observation could also be useful in potential cell therapy for X-linked disorders such as Rett Syndrome as the differentiated cells derived from iPS cells expressing the normal protein could possibly be transplanted back in place of those expressing the mutant protein.

“For studies of X-linked diseases with female iPS cells, one needs to be careful about which X chromosome is expressed,” Plath said.

The study was funded by the California Institute for Regenerative Medicine, the National Institutes of Health and the UCLA Broad Stem Cell Research Center.

The stem cell center was launched in 2005 with a UCLA commitment of $20 million over five years. A $20 million gift from the Eli and Edythe Broad Foundation in 2007 resulted in the renaming of the center. With more than 200 members, the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research is committed to a multi-disciplinary, integrated collaboration of scientific, academic and medical disciplines for the purpose of understanding adult and human embryonic stem cells. The center supports innovation, excellence and the highest ethical standards focused on stem cell research with the intent of facilitating basic scientific inquiry directed towards future clinical applications to treat disease. The center is a collaboration of the David Geffen School of Medicine, UCLA’s Jonsson Cancer Center, the Henry Samueli School of Engineering and Applied Science and the UCLA College of Letters and Science. To learn more about the center, visit our web site at http://www.stemcell.ucla.edu. To learn more about the center, visit our web site at http://www.stemcell.ucla.edu.

Kim Irwin | Newswise Science News
Further information:
http://www.ucla.edu

More articles from Life Sciences:

nachricht Unique genome architectures after fertilisation in single-cell embryos
30.03.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Researchers shoot for success with simulations of laser pulse-material interactions

29.03.2017 | Materials Sciences

Igniting a solar flare in the corona with lower-atmosphere kindling

29.03.2017 | Physics and Astronomy

As sea level rises, much of Honolulu and Waikiki vulnerable to groundwater inundation

29.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>