One of the key circuits in regulating genes involved in producing blood stem cells is deciphered

Researchers from the group on stem cells and cancer at IMIM (Hospital del Mar Medical Research Institute) have deciphered one of the gene regulation circuits which would make it possible to generate hematopoietic blood cells, i.e. blood tissue stem cells. This finding is essential to generate these cells in a laboratory in the future, a therapy that could benefit patients with leukaemia or other diseases who need a transplant and who, in many cases, do not have a compatible donor.

In the process of generating stem cells, many molecule signals intervene which, through a regulating circuit are induced at a certain moment and remain active during a specific time until they switch off so these cells can differentiate. Anna Bigas, the coordinator of the research group on stem cells and cancer at IMIM explains: "We discovered that the Notch protein, which is involved in the development of most tissues, is responsible for activating the gene GATA2 which is necessary to generate hematopoietic stem cells; at the same time, it induces the reproduction of its own repressor, HES-1". The team lead by Bigas has also shown that this regulating circuit allows the limited production of GATA2, and this is essential for the production of hematopoietic stem cells.

The study was developed over 4 years and consisted in performing a large number of experiments with the collaboration of groups from Japan, Holland and the USA. On the one hand, researchers identified the mechanism regulating the gene GATA2 in hematopoietic stem cells of a and, on the other hand, they identified regulating this gene; i.e. the sequences of gene GATA2 where the Notch protein and the repressor HES-1 bind. After generating several in these sequences, researchers saw that if the Notch protein does not bind to GATA 2, the gene is not activated, whereas if it's the HES-1 that doesn't bind to it, then there is an over-production of the GATA 2. Researchers also proved that where HES-1 has been eliminated may not generate functional hematopoietic stem cells due to excessive production of GATA 2.

One of the difficulties encountered by the researchers when carrying out this study is that, from a methodological approach, some of the required techniques were not possible to carry out at IMIM's laboratories, and for this reason collaboration was established with the group lead by Prof. Masayuki Yamamoto at the Tohoku University School of Medicine in Sendai, Japan. The first signatory of the paper, Dr. Jordi Grau, travelled to Sendai for four months but, due to the earthquake in 2011, it was impossible to conclude the task. It was thanks to the collaborations established with the group lead by Prof. Elaine Dzierzak at the Erasmus University in Rotterdam that it was finally possible to continue with the project.

The process of generating stem cells specifically from tissue in a laboratory is being studied in many laboratories around the world, but this has not yet been achieved. This shows that we need further research into the mechanisms used be the embryo to generate these cells and which regulating genes are involved in this process. "We discovered a basic circuit but there are still many more to discover. Our end objective is to validate our results with cells coming from mouse embryonic stem cells and then being able to use this knowledge to generate human in a laboratory for therapeutic purposes. These cells could then be used for patients needing a hematologic transplant and do not have a compatible donor" concludes Dr. Bigas.

More information: "Hes repressors are essential regulators of Hematopoietic Stem Cell Development downstream of Notch signaling". Jordi Guiu, Ritsuko Shimizu, Teresa D'Altri, Stuart T. Fraser &, Jun Hatakeyama, Emery H.Bresnick, Ryoichiro Kageyama, Elaine Dzierzak, Masayuki Yamamoto, Lluis Espinosa and Anna Bigas. Journal of Experimental Medicine. jem.rupress.org/content/210/1/71.full.pdf+html

add to favorites email to friend print save as pdf

Related Stories

Study unlocks origins of blood stem cells

Dec 09, 2011

A research team led by Nancy Speck, PhD, professor of Cell and Developmental Biology at the Perelman School of Medicine at the University of Pennsylvania, has discovered a molecular marker for the immediate ...

Recommended for you

Science of romantic relationships includes gene factor

13 hours ago

(Medical Xpress)—Adolescents worry about passing tests, winning games, lost phones, fractured bones—and whether or not they will ever really fall in love. Three Chinese researchers have focused on that ...

Stress reaction may be in your dad's DNA, study finds

Nov 21, 2014

Stress in this generation could mean resilience in the next, a new study suggests. Male mice subjected to unpredictable stressors produced offspring that showed more flexible coping strategies when under ...

More genetic clues found in a severe food allergy

Nov 21, 2014

Scientists have identified four new genes associated with the severe food allergy eosinophilic esophagitis (EoE). Because the genes appear to have roles in other allergic diseases and in inflammation, the ...

Brain-dwelling worm in UK man's head sequenced

Nov 20, 2014

For the first time, the genome of a rarely seen tapeworm has been sequenced. The genetic information of this invasive parasite, which lived for four years in a UK resident's brain, offers new opportunities ...

User comments

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.