Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cell memory loss enables the production of stem cells

15.12.2015

Scientists identify a molecular key that helps cells maintain identity and prevents the conversion of adult cells into induced pluripotent stem cells

They say we can't escape our past--no matter how much we change, we still have the memory of what came before; the same can be said of our cells.


Induced pluripotent stem cell (iPS cell) colonies were generated after researchers at Harvard Stem Cell Institute suppressed the CAF1 gene.

Credit: Sihem Chaloufi

Adult cells, such as skin or blood cells, have a cellular "memory," or record of how the cell changes as it develops from an uncommitted embryonic cell into a specialized adult cell. Now, Harvard Stem Cell Institute researchers at Massachusetts General Hospital (MGH) in collaboration with scientists from the Research Institutes of Molecular Biotechnology (IMBA) and Molecular Pathology (IMP) in Vienna have identified genes that when suppressed effectively erase a cell's memory, making the cell more susceptible to reprogramming and, consequently, making the process of reprogramming quicker and more efficient.

The study was recently published in Nature.

"We began this work because we wanted to know why a skin cell is a skin cell, and why does it not change its identity the next day, or the next month, or a year later?" said co-senior author Konrad Hochedlinger, PhD, an HSCI Principal Faculty member at MGH and Harvard's Department of Stem Cell and Regenerative Biology, and a world expert in cellular reprogramming.

Every cell in the human body has the same genome, or DNA blueprint, explained Hochedlinger, and it is how those genes are turned on and off during development that determines what kind of adult cell each will become. By manipulating those genes and introducing new factors, scientists can unlock dormant parts of an adult cell's genome and reprogram it into another cell type.

However, "a skin cell knows it is a skin cell," said IMBA's Josef Penninger, even after scientists reprogram those skin cells into induced pluripotent stem cells (iPS cells) - a process that would ideally require a cell to "forget" its identity before assuming a new one. Cellular memory is often conserved, acting as a roadblock to reprogramming. "We wanted to find out which factors stabilize this memory and what mechanism prevents iPS cells from forming," Penninger said.

To identify potential factors, the team established a genetic library targeting known chromatin regulators -- genes that control the packaging and bookmarking of DNA, and are involved in creating cellular memory.

Hochedlinger and Sihem Cheloufi, co-first author and a postdoc in Hochedlinger's lab, designed a screening approach that tested each of these factors.

Of the 615 factors screened, the researchers identified four chromatin regulators, three of which had not yet been described, as potential roadblocks to reprogramming. In comparison to the three to four fold increase seen by suppressing previously known roadblock factors, inhibiting the newly described CAF1 (chromatin assembly factor 1) made the process 50 to 200 fold more efficient. Moreover, in the absence of CAF1 reprogramming turned out to be much faster: While the process normally takes nine days, the researchers could detect the first iPS cell after four days.

"The CAF1 complex ensures that during DNA replication and cell division daughter cells keep their memory, which is encoded on the histones that the DNA is wrapped around," said Ulrich Elling, a co-first author from IMBA. "When we block CAF-1, daughter cells fail to wrap their DNA the same way, lose this information and covert into blank sheets of paper. In this state, they respond more sensitively to signals from the outside, meaning we can manipulate them much more easily."

By suppressing CAF-1 the researchers were also able to facilitate the conversion of one type of adult cell directly into another, skipping the intermediary step of forming iPS cells, via a process called direct reprogramming, or transdifferentiation. Thus, CAF-1 appears to act as a general guardian of cell identity whose depletion facilitates both the interconversion of one adult cell type to another as well as the conversion of specialized cells into iPS cells.

In finding CAF-1, the researchers identified a complex that allows cell memory to be erased and rewritten. "The cells forget who they are, making it easier to trick them into becoming another type of cell," said Sihem Cheloufi.

CAF-1 may provide a general key to facilitate the "reprogramming" of cells to model disease and test therapeutic agents, IMP's Johannes Zuber explained. "The best-case scenario," Zuber said, "is that with this insight, we hold a universal key in our hands that will allow us to model cells at will."

Media Contact

BD Colen
bd_colen@harvard.edu
617-495-7821

 @HarvardMed

http://hms.harvard.edu 

BD Colen | EurekAlert!

Further reports about: DNA Harvard cell type daughter cells iPS cells memory loss skin skin cell stem cells

More articles from Life Sciences:

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>