Differentiated blood cells were reprogrammed into hematopoietic
Researchers at the Boston Children's Clinic, working under the guidance of Dr. Derrick J. Rossi, reprogrammed mouse blood cells into stem cells using a cocktail of 8 genetic switches – the so-called transcription factors. The resulting cells, called induced hematopoietic stem cells (IGSCS), have the ability to self-replicate and differentiate into all cellular components of the blood.
Usually hematopoietic (hematopoietic) stem cells for transplantation are isolated from bone marrow, peripheral blood mobilized by growth factors, or from umbilical cord blood. The success of therapy strongly depends on the cellular nature of the graft, but the number of hematopoietic cells in the body is very limited. According to Rossi, only 1 out of 20,000 bone marrow cells is hematopoietic. Therefore, the possibility of obtaining autologous hematopoietic stem cells from other patient cells would make a revolution in transplant medicine.
As part of their study, the authors screened gene expression in 40 different types of blood cells and hematopoietic progenitor cells of mice. As a result, they identified 36 transcription factors – genes that control the activation and inactivation of other genes – that were expressed exclusively in hematopoietic stem cells and disappeared at subsequent stages of their differentiation.
During a series of experiments on mice, they found that a complex containing six of these 36 factors – Hlf, Runx1t1, Pbx1, Lmo2, Zfp37 and Prdm5 – and two initially unidentified factors – Mycn and Meis1 – provided stable reprogramming of committed (irreversibly differentiated in the direction of a particular hematopoietic germ) myeloid and lymphoid progenitor cells in iGSC.
The researchers managed to achieve this result by treating target cells with viral vectors - carriers of genes encoding all 8 transcription factors and a molecular switch that activated them in the presence of doxycycline. The cells obtained as a result of reprogramming were injected into mice, the addition of doxycycline to their feed activated the corresponding genes.
A subsequent analysis of the blood cells of the recipient animals showed that the transplanted cells differentiated into all cellular components of the blood. Stem cells isolated from the bone marrow of recipient mice, in turn, successfully restored the blood composition of secondary recipients. This indicates that reprogrammed cells have the ability to self-renew for a long time.
However, the results obtained at the current stage are very far from being implemented into clinical practice. Researchers have yet to find out the contribution made to the reprogramming process by each of the eight transcription factors, as well as the possibility of obtaining similar results without using viral vectors and transcription factors. Moreover, it is still unclear whether it will be possible to achieve the desired result when working with human cells, and also whether it is possible to obtain iGSC by reprogramming other cells of the body.
Article by Jonah Riddell et al. Reprogramming Committed Murine Blood Cells to Induced Hematopoietic Stem Cells with Defined Factors is published in the journal Cell.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of ScienceDaily:
Blood cells reprogrammed into blood stem cells in mice.
28.04.2014