Researchers redefine how blood is made.


In human blood formation, everything begins with the stem cell, which is the executive decision-maker quickly driving the process that replenishes blood at a daily rate that exceeds 300 billion cells.  Red blood cells, most white blood cells, and platelets are produced in the bone marrow, the soft fatty tissue inside bone cavities. Two types of white blood cells, T and B cells (lymphocytes), are also produced in the lymph nodes and spleen, and T cells are produced and mature in the thymus gland.

Within the bone marrow, all blood cells originate from a single type of stem cell. When the stem cell divides, it first becomes an immature red blood cell, white blood cell, or platelet-producing cell. The immature cell then divides, matures further, and ultimately becomes a mature red blood cell, white blood cell, or platelet, or so it was thought.  Now, a study from researchers at the University of Toronto have discovered a completely new view of how human blood is made, upending the conventional doctrine from the 1960s.  The team state that the findings prove the classic ‘textbook’ view doesn’t actually exist.  The study is published in the journal Science.

Earlier studies from the group isolated a human blood stem cell in its purest form, as a single stem cell capable of regenerating the entire blood system.  Four years ago, when they isolated the pure stem cell, the researchers realized they had also uncovered populations of stem-cell like ‘daughter’ cells that they presumed were other types of stem cells.  However, when the team burrowed further to study these ‘daughters’, they discovered they were actually already mature blood lineages. In other words, lineages that had broken off almost immediately from the stem cell compartment and had not developed downstream through the slow, gradual ‘textbook’ process.  The current study finally resolves how different kinds of blood cells form quickly from the stem cell and not further downstream as has been traditionally thought.

The current study topples the textbook view that the blood development system is stable once formed. Data findings show that the blood system is two-tiered and changes between early human development and adulthood.  Results show that in redefining the architecture of blood development, the lineage potential of nearly 3,000 single cells were mapped from 33 different cell populations of stem and progenitor cells obtained from human blood samples taken at various life stages and ages.

To achieve this the lab developed a cell-sorting scheme to resolve myeloid, erythroid, and megakaryocytic fates from single CD34+ cells and then mapped the progenitor hierarchy across human development. Results show that fetal liver contained large numbers of distinct oligopotent progenitors with intermingled myeloid, erythroid, and megakaryocytic fates. In contrast, data findings show that few oligopotent progenitor intermediates were present in the adult bone marrow, instead only two progenitor classes predominate, multipotent and unipotent, with erythroid-megakaryocytic lineages emerging from multipotent cells.

The lab state that their discovery means the global medical community will be able to understand a wide variety of human blood disorders and diseases far better, from anemia, where there are not enough blood cells, to leukemia, where there are too many blood cells.  They go on to add that there are also promising implications for advancing the global quest in regenerative medicine to manufacture mature cell types such as platelets or red blood cells by engineering cells, a process known as inducing pluripotent stem cells.  They have provided a video detailing their discovery and its applications here.

The team surmise that the developmental shift to an adult ‘two-tier’ hierarchy challenges the current doctrine and provides a revised framework to understand normal and disease states of human hematopoiesis. For the future, the researchers state that human donors are the sole source of platelets which cannot be stored or frozen; by combining the ability to optimize induced pluripotent stem cells with these newly identified progenitors that give rise only to platelets and red blood cell, they will be able to develop better methods to generate these mature cells.

Source:  University Health Network (UHN)

 

Bone marrow, coloured scanning electron micrograph (SEM). This freeze-fracture has revealed the cavity (lumen) of a large venous sinus (pink), which contains mature blood cells (red), and developing white blood cells (blue). Either side of the sinus are the haemopoetic foci of the marrow (green). Magnification: x3000 when printed at 10 centimetres across.  Credit: STEVE GSCHMEISSNER/SCIENCE PHOTO LIBRARY.

Bone marrow, coloured scanning electron micrograph (SEM). This freeze-fracture has revealed the cavity (lumen) of a large venous sinus (pink), which contains mature blood cells (red), and developing white blood cells (blue). Either side of the sinus are the haemopoetic foci of the marrow (green). Magnification: x3000 when printed at 10 centimetres across. Credit: STEVE GSCHMEISSNER/SCIENCE PHOTO LIBRARY.

 

 

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