Biology Reference
In-Depth Information
Stem cells
Progenitors
Mature
Term.Diff.
miRNAs
miRNAs
miRNAs
miRNAs
A
Steady state
GMP
Granulocyte
CMP
Monocyte
Megakaryocyte
HSC MPP
RBC
MEP
CLP
B lymphocyte
T lymphocyte
B
“Inflammatory hematopoiesis”
Granulocyte
GMP
Cancer
CMP
Monocyte
HSC
cycling
MPP
Megakaryocyte
RBC
MEP
CLP
B lymphocyte
T lymphocyte
Figure 6.2
Steady-state and “Inflammatory hematopoiesis”—(A) Mammalian hema-
topoiesis in the bone marrow begins with the hematopoietic stem cell (HSC) which
gives rise to progenitors that continue to develop into lineage-restricted progeny.
Ultimately, cells reach maturity and become terminally differentiated. miRNAs have
been shown to play important regulatory roles at the different stages of blood cell
development. (B) The hematopoietic process is sensitive to inflammatory stress caused
by microbial infection or elevations in specific types of cytokines. During “inflamma-
tory hematopoiesis,” the HSC increases its cell cycle rate and produces more progeni-
tors with a bias toward making granulocyte and monocyte progeny at the expense of
other cell lineages. This condition also resembles that observed during preleukemia
suggesting a link between “inflammatory hematopoiesis” and cancer. Several miRNAs
have also been implicated in the regulation of this process. MPP, multipotent progeni-
tor; CMP, common myeloid progenitor; CLP, common lymphoid progenitor; GMP,
granulocyte-monocyte progenitor; MEP, megakaryocyte-erythroid progenitor; RBC,
red blood cell.
understood. How miRNAs are integrated into the molecular networks
governing these decisions, as they have been shown to be in embryonic
stem cells (
Melton
et al
., 2010
), is still under investigation.
HSCs first arise during embryonic development and continue to ensure
blood production throughout adulthood. However, the HSC does not have
an unchanging phenotype. As mice age, they progressively alter the output
of
their HSCs,
favoring progeny cells of
the myeloid lineage while
