Hematopoietic Stem Cells Self-Renewal

Hematopoietic Stem Cells Division

The ability to divide symmetrically to generate identical daughters is a feature of most cells, including hematopoietic stem cells. However, the multipotent stem cell possesses an added ability to undergo asymmetric cell divisions, yielding one committed progenitor daughter and one stem cell daughter, or two differentiating progeny; regulating the balance between symmetric and asymmetric stem cell divisions becomes critical in maintaining proper hematopoietic stem cell numbers and in meeting the demand for differentiated cells. A question related to the previous discussion of whether intrinsic or extrinsic factors determine hematopoietic stem cell lineage fate, is whether intrinsic or extrinsic factors determine the possible outcomes for a dividing hematopoietic stem cells (two hematopoietic stem cell progeny [stem cell expansion], one hematopoietic stem cell and one differentiating cell [a self-renewal division], or two differentiating progeny).

It is clear that feedback mechanisms exist that govern the size of the stem cell pool, as following myeloablation and transplantation of a limited number of hematopoietic stem cells the pool expands toward that seen in a normal individual but not beyond, even when subjected to forced overexpression of genes that enhance hematopoietic stem cell expansion.

Limitation on hematopoietic stem cells Expansion

Hematopoietic stem cells do not appear to have a limit on their capacity for expansion; experiments using serial transplantation of marrow cells revealed that even after four such maneuvers the transplantation of a limiting number of hematopoietic stem cells was associated with a tenfold expansion in the recipient, a level of expansion remarkably consistent from one serial transplant to the next. Thus, there does not appear to be an intrinsic limit on hematopoietic stem cell expansion that sets the size of the stem cell pool. Rather, evidence from quantitative transplants suggests that there exist both intrinsic and extrinsic controls on the size of the stem cell pool.