Biology Reference
In-Depth Information
prevent bleeding by clotting, and mediate inflammatory reactions. Because the
hematopoietic system plays such a central role in human diseases such as
infections, cancer, autoimmunity, and anemia, it has been intensely studied for
more than a century. This scrutiny has helped to shape many of the developmen-
tal paradigms that exist today and has identified specific protein factors that
serve as master regulators of blood cell lineage specification. Despite this
progress, many aspects of blood cell development remain obscure, suggesting
that novel layers of regulation must exist. Consequently, the emergence of
regulatory noncoding RNAs, such as the microRNAs (miRNAs), is beginning to
provide new insights into the molecular control networks underlying hematopoi-
esis and diseases that stem from aberrations in this process. This review will
discuss how miRNAs fit into our current understanding of hematopoietic devel-
opment inmammals and howbreakdowns in these pathways can trigger disease.
1. Introduction
During embryogenesis, blood cell development takes place in the yolk
sac, placenta, and fetal liver. Shortly after birth, the primary site of hemato-
poiesis shifts to the bone marrow, where it remains throughout adulthood.
Production of 10
11
-10
12
new blood cells must take place daily to maintain
homeostatic levels in adult humans. Mature blood cells are made up of many
different lineages that carry out diverse functions such as providing immu-
nity against pathogens, carrying oxygen throughout the body, and mediat-
ing the process of clotting. The hematopoietic system is central to
mammalian life and is involved either directly or indirectly in most
human diseases. Thus, this elegant developmental system warrants the
amount of study that has and will continue to go into understanding its
intricate processes.
Hematopoietic differentiation is the quintessential stem cell-driven
developmental process (
Orkin and Zon, 2008
). In this, a self-renewing
stem cell population spawns offspring that change their properties in a
bifurcating process of specification leading to a myriad of ultimate cell
products. Thus, the process involves a cascade of cell choices. From the
years of effort that have gone into understanding these developmental
choices, we have learned that protein-coding genes are critical regulators
of these cell fate decisions, as they are throughout mammalian development
(
Orkin and Zon, 2008
;
Robb, 2007
). Cellular decisions such as self-renewal
versus differentiation, proliferation versus quiescence, and survival versus
death have all been shown to involve specific sets of proteins. Despite this
knowledge, many aspects of hematopoietic development and mature blood
cell function remain unclear. Now, with the identification of noncoding
(nc) RNAs, and in particular miRNAs, many unanswered questions about
hematopoietic development are beginning to be answered.
