TY  - JOUR
A1  - Ahmad, Ruhel
A1  - Wolber, Wanja
A1  - Eckardt, Sigrid
A1  - Koch, Philipp
A1  - Schmitt, Jessica
A1  - Semechkin, Ruslan
A1  - Geis, Christian
A1  - Heckmann, Manfred
A1  - Brüstle, Oliver
A1  - McLaughlin, John K.
A1  - Sirén, Anna-Leena
A1  - Müller, Albrecht M.
T1  - Functional Neuronal Cells Generated by Human Parthenogenetic Stem Cells
JF  - PLoS One
N2  - Parent of origin imprints on the genome have been implicated in the regulation of neural cell type differentiation. The ability of human parthenogenetic (PG) embryonic stem cells (hpESCs) to undergo neural lineage and cell type-specific differentiation is undefined. We determined the potential of hpESCs to differentiate into various neural subtypes. Concurrently, we examined DNA methylation and expression status of imprinted genes. Under culture conditions promoting neural differentiation, hpESC-derived neural stem cells (hpNSCs) gave rise to glia and neuron-like cells that expressed subtype-specific markers and generated action potentials. Analysis of imprinting in hpESCs and in hpNSCs revealed that maternal-specific gene expression patterns and imprinting marks were generally maintained in PG cells upon differentiation. Our results demonstrate that despite the lack of a paternal genome, hpESCs generate proliferating NSCs that are capable of differentiation into physiologically functional neuron-like cells and maintain allele-specific expression of imprinted genes. Thus, hpESCs can serve as a model to study the role of maternal and paternal genomes in neural development and to better understand imprinting-associated brain diseases.
KW  - methylation
KW  - derivation
KW  - blastocysts
KW  - pluripotent
KW  - differentiation
KW  - lines
KW  - brain development
KW  - in-vitro
KW  - mice
KW  - specification
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130268
VL  - 7
IS  - 8
ER  - 
TY  - JOUR
A1  - Schmitt, Jessica
A1  - Eckardt, Sigrid
A1  - Schlegel, Paul G
A1  - Sirén, Anna-Leena
A1  - Bruttel, Valentin S
A1  - McLaughlin, K John
A1  - Wischhusen, Jörg
A1  - Müller, Albrecht M
T1  - Human parthenogenetic embryonic stem cell-derived neural stem cells express HLA-G and show unique resistance to NK cell-mediated killing
JF  - Molecular Medicine
N2  - Parent-of-origin imprints have been implicated in the regulation of neural differentiation and brain development. Previously we have shown that, despite the lack of a paternal genome, human parthenogenetic (PG) embryonic stem cells (hESCs) can form proliferating neural stem cells (NSCs) that are capable of differentiation into physiologically functional neurons while maintaining allele-specific expression of imprinted genes. Since biparental ("normal") hESC-derived NSCs (N NSCs) are targeted by immune cells, we characterized the immunogenicity of PG NSCs. Flow cytometry and immunocytochemistry revealed that both N NSCs and PG NSCs exhibited surface expression of human leukocyte antigen (HLA) class I but not HLA-DR molecules. Functional analyses using an in vitro mixed lymphocyte reaction assay resulted in less proliferation of peripheral blood mononuclear cells (PBMC) with PG compared with N NSCs. In addition, natural killer (NK) cells cytolyzed PG less than N NSCs. At a molecular level, expression analyses of immune regulatory factors revealed higher HLA-G levels in PG compared with N NSCs. In line with this finding, MIR152, which represses HLA-G expression, is less transcribed in PG compared with N cells. Blockage of HLA-G receptors ILT2 and KIR2DL4 on natural killer cell leukemia (NKL) cells increased cytolysis of PG NSCs. Together this indicates that PG NSCs have unique immunological properties due to elevated HLA-G expression.
KW  - brain development
KW  - immune response
KW  - T lymphocytes
KW  - blastocysts
KW  - lines
KW  - HLA-G gene
KW  - mhc molecules
KW  - nervous system
KW  - in vitro
KW  - stem/progenitor cells
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-149170
VL  - 21
IS  - 2101185
ER  -