Download Embryonic Stem Cells in Primates by Parthenogenesis

Embryonic Stem Cells in Primates
by Parthenogenesis
Graduate Studies
Department of Physiology
MICHIGAN STATE UNIVERSITY
Jose Cibelli, Ph.D.
Biparental primate embryonic stem (ES) cells have the potential to become any cell type of the adult body. We have
recently created parthenogenetic non-human primate ES cells (Cyno-1) from a Cynomolgus macaque female. Teratomas
from these cells differentiate preferentially to ectoderm and endoderm-derived cells. Mesoderm derived cells are present
only in limited numbers. By definition these cells lack any paternal contribution to their genome, thus it is likely that their
imprinting status significantly differs from biparental ES cell lines and is presumably responsible for their altered
differentiation capacity in comparison to biparental cells.
The long-term goal of our work is to understand the differentiation processes
that occur in parthenogenetic ES cells. Our studies are directed at the overall
patterns of gene expression and how they change as differentiation occurs. We
are comparing global gene expression patterns of undifferentiated and
differentiated Cyno-1 cells with that of primate embryonic stem cells derived
from fertilized embryos, with particular emphasis on the role of imprinted genes.
This information will help us understand phenotypic differences in
monoparental and biparental primate ES cells and gene expression cascades
associated with cell differentiation that are potentially influenced by imprinting
status.
Figure 1
To date, parthenogenetic ES cells are the only source of autologous ES cells known in non-human primates. We have
shown that these cells are capable of producing a variety of tissues, but not all tissues of the body. We hypothesize that
undifferentiated Cyno-1 ES cells have deregulated gene expression of imprinted genes and that upon differentiation,
imprinted genes in Cyno-1 ES cells become faithful
A
B
C
to their parthenogenetic origin. We also
hypothesize that a more homogeneous in vivo
differentiation of Cyno-1 ES cells can be achieved
by modulating the expression of imprinted genes.
By characterizing Cyno-1 ES cells at the molecular
and cellular level using innovative approaches, we
hope to understand the role of gene imprinting in
D
F
EE
parthenogenetic
primate
ES
cells
during
differentiation and development.
G
H
I
This new knowledge will be used to obtain
parthenogenetic ES cells with the capacity to form
all tissues in the body. Eventually, we could
develop a model to treat human diseases using
these autologous ES cells. If feasible, this could be
a unique unlimited source of autologous cells,
offering a valid alternative to the ethical and
scientific challenges that embryonic stem cells
isolated from fertilized embryos pose.
Figure 1. Cyno-1 ES cells.
Figure 2. Teratoma differentiation of Cyno-1 cells. Tumor in the peritoneal cavity (A), smooth muscle and intestinal
epithelia (B), skin (C), intestine (D) hair follicle (E), ganglia (F), melanocytes surrounded by neuronal tissue
(G), bone (H) and cartilage (I).