Biomedical Engineering Reference
In-Depth Information
Chapter 8
Stem Cell Renewal and Differentiation
This topic fi lls a much-needed gap.
- Moses Hadas
Among the most investigated are the mechanisms that regulate stem cell function in
the nervous and hematopoietic systems. Therefore, hematopoietic stem cells, which
give rise to all blood and immune system cells, and neural crest stem cells, which
give rise to the peripheral nervous system, are among the best-characterized stem
cells. We are just beginning to understand how their functions are regulated. The
conserved mechanisms have long been hypothesized as the mode of stem cell regu-
lation. However, testing this requires interdisciplinary approaches. The ultimate
goal is to integrate what we know about stem cells in different tissues to understand
the extent to which they employ similar or different mechanisms to regulate critical
functions. We have focused so far on the mechanisms that regulate stem cell self-
renewal, aging, and their role in organogenesis.
Stem Cell Self-Renewal: Regulation
Persistence of stem cells which are maintained in numerous adult tissues by self-
renewal (stem cells dividing to make more stem cells) raises the question of whether
this process is regulated by mechanisms that are conserved between tissues.
It was found that the polycomb family transcriptional repressor Bmi-1 is required
for the self-renewal but not for the differentiation of stem cells in the hematopoietic
system and peripheral and central nervous systems [ 1 ]. In each case, stem cells are
formed in normal numbers during fetal development but exhibit impaired self-
renewal and become depleted postnatally. Bmi-1 promotes stem cell self-renewal
partly by repressing p16 Ink4a , a cyclin-dependent kinase inhibitor, and p19 Arf , a p53
agonist. Both of these checkpoint proteins negatively regulate cell proliferation, and
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