28 November 2013

The secret of immortality of hematopoietic cells has been revealed

The hematopoietic, or hematopoietic, stem cells contained in the red bone marrow are at the top of a complex cellular hierarchy. These cells actively divide and give rise to all types of blood cells: erythrocytes, leukocytes and platelets. To ensure constant renewal of the cellular composition of the blood, the bone marrow must produce about a million of these "daughter" cells every second.

For many years, experts have been concerned about the question: what ensures the ability of hematopoietic stem cells to maintain the ability to actively divide and differentiate for decades, while differentiated blood cells live only a few weeks or months. Recently, researchers from the University of Pennsylvania, working under the guidance of Professor Dennis Disher (Dennis Discher), managed to decipher one of the mechanisms underlying this unique ability.

The generally accepted theory explains this "almost immortality" by the ability to asymmetric division, in which one of the daughter cells retains all the qualities of the maternal stem cell. However, the mechanism providing this ability has remained a mystery until now. In search of its solution, the researchers analyzed all the genes expressed by hematopoietic stem cells and their most actively dividing descendants. They suggested that the key factor of asymmetric division may be proteins localized only on one side of the dividing cell.

The experiments revealed different expression profiles of the myosin II protein, which exists in two different forms: A and B. Myosin II provides contractility of muscle cells, and in non-contracting cells it participates in the process of cutting and joining the cell wall during cell division in two.

It turned out that hematopoietic stem cells contain two forms of myosin II, whereas mature erythrocytes and leukocytes contain only form A. Based on this, the authors suggested that myosin IIB is the key factor in the mechanism under study.

To confirm the hypothesis, they labeled the main proteins of dividing stem cells with different dyes and placed them under a microscope. Subsequent observation confirmed that myosin IIB moves to one half of the dividing cell, which after division forms a new stem cell.


Dividing hematopoietic stem cell. Myosin IIB (marked green)
concentrated in the part that will remain stem.

When human hematopoietic stem cells were injected into mice, in which the production of myosin IIB was blocked using genetic methods, scientists demonstrated that, despite the incessant division of stem cells and their early descendants in the bone marrow, the number of mature cells in the blood of animals progressively decreased.

At the same time, blocking the production of both forms of myosin II with the help of a pharmacological drug increased the number of "resting" stem cells in the bone marrow of animals.

The researchers believe that the data obtained can form the basis of methods for restoring hematopoietic stem cells after chemotherapy or even for "growing" blood preparations in the laboratory.

Moreover, currently available drugs that block the production of myosin IIB can be used to enrich bone marrow transplants with hematopoietic stem cells due to their symmetrical division.

Article by Jae-Won Shin et al. Contractile Forces Sustain and Polarize Hematopoiesis from Stem and Progenitor Cells is published in the journal Cell Stem Cell.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the University of Pennsylvania:
Researchers at Penn Uncover Mechanism Behind Blood Stem Cells’ Longevity.

28.11.2013

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