Stem cells are units of natural selection for tissue formation, for germline
development, and in cancer development
#MMPMID26195745
Weissman IL
Proc Natl Acad Sci U S A
2015[Jul]; 112
(29
): 8922-8
PMID26195745
show ga
It is obvious that natural selection operates at the level of individuals and
collections of individuals. Nearly two decades ago we showed that in
multi-individual colonies of protochordate colonial tunicates sharing a blood
circulation, there exists an exchange of somatic stem cells and germline stem
cells, resulting in somatic chimeras and stem cell competitions for gonadal
niches. Stem cells are unlike other cells in the body in that they alone
self-renew, so that they form clones that are perpetuated for the life of the
organism. Stem cell competitions have allowed the emergence of competitive
somatic and germline stem cell clones. Highly successful germline stem cells
usually outcompete less successful competitors both in the gonads of the genotype
partner from which they arise and in the gonads of the natural parabiotic
partners. Therefore, natural selection also operates at the level of germline
stem cell clones. In the colonial tunicate Botryllus schlosseri the formation of
natural parabionts is prevented by a single-locus highly polymorphic
histocompatibility gene called Botryllus histocompatibility factor. This limits
germline stem cell predation to kin, as the locus has hundreds of alleles. We
show that in mice germline stem cells compete for gonad niches, and in mice and
humans, blood-forming stem cells also compete for bone marrow niches. We show
that the clonal progression from blood-forming stem cells to acute leukemias by
successive genetic and epigenetic events in blood stem cells also involves
competition and selection between clones and propose that this is a general theme
in cancer.
free
free
free
