Oxygen Model of Every Disease

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Majid Ali, M.D.

Oxygen Governs the Production and Functions of growth factors, Which Preserve the Health of Cell Populations of the Body.


“It seems that growth factors may instruct blood-cell progenitors to develop into specific mature cell types, actively determining lineage choice. But is this reductionist view of cell fate overly simplistic?”

 The above quote is taken from an article in the journal Nature (2009;461:183, September 9, 2009. Below, I include some more text from that article.


The nature-versus-nurture debate about human potential will be familiar to most. A similar dispute surrounds the role of environmental signals, such as growth factors, in determining cell-type identity in multicellular organisms. Two papers, one by Rieger et al.1 published in Science, and the other by Sarrazin et al.2 in Cell, inform this discussion by providing evidence that environmental cues might actively determine cell lineage.

The process of lineage specification is fundamental to the development and maintenance of tissues in multicellular organisms. Blood formation, or haematopoiesis, exemplifies this. Here, rare multipotent stem cells and progenitor cells that reside in the bone marrow produce several different lineages of mature blood cell. In steady-state conditions, haematopoiesis accommodates a ferociously high rate of cell turnover, with millions of cells being generated every second. In addition, blood cells are produced at speed ‘on demand’ in response to injury or challenge — for instance, red blood cells in response to bleeding or white blood cells in response to infection.

With a myriad of defined cellular intermediates along any lineage pathway3, 4, and a battery of functional assays enabling studies of the generation of different blood-cell lineages from single stem cells and progenitor cells3, 4, 5, the blood system has for decades provided a playground for exploring mechanisms of lineage specification. From this work an impressive list of nuclear, cytoplasmic and extracellular regulators of blood-cell development have been identified and characterized3, 4, of which some growth factors (termed cytokines) are routinely used in the clinic to replenish specific types of blood cell5. These growth factors function by selectively enhancing the proliferation and differentiation of progenitors that are already restricted in their lineage options, and by improving the function of their mature descendants. However, the patterns of expression of growth-factor receptors on multipotent blood-cell progenitors, and their responsiveness to these factors5, suggest that growth factors might also target multipotent progenitors or stem cells at a pre-committed stage, possibly by affecting their lineage choice per se.

The unresolved question therefore is whether environmental or extrinsic cues such as growth factors usually instruct multipotent progenitors to commit to a particular lineage — the ‘instructive’ model (Fig. 1a, overleaf); or whether these cues simply support the survival and proliferation of cells that have already committed to a specific lineage by a cell-autonomous or intrinsic agency — the ‘selective’ or ‘permissive’ model (Fig. 1b). This question is by no means new, and evidence has been provided (and debated) in support of permissive5, 6, 7 and instructive5, 8, 9 actions of cytokines in determining blood-cell-lineage commitment.

Part of the reason that this issue has been difficult to address is that the outcome measured in these studies — the production of lineage-specified cells — is the same whether regimes are instructive or selective (Fig. 1). To unequivocally distinguish between instructive and selective effects on lineage development, one must account for the fate, be it survival and proliferation, death or quiescence, of every daughter cell of an uncommitted progenitor cell that has more than one lineage potential.

For readers with biology background, below I reproduce some text from an article in the journal Nature (2009;461:183, September 9, 2009(

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growth factors (termed cytokines) are routinely used in the clinic to replenish specific types of blood cell5. These growth factors function by selectively enhancing the proliferation and differentiation of progenitors that are already restricted in their lineage options, and by improving the function of their mature descendants. However, the patterns of expression of growth-factor receptors on multipotent blood-cell progenitors, and their responsiveness to these factors5, suggest that growth factors might also target multipotent progenitors or stem cells at a pre-committed stage, possibly by affecting their lineage choice per se.

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