To realize cell transplantation therapy for Parkinson's disease (PD), the grafted neurons should be integrated into the host neuronal circuit in order to restore the lost neuronal function. Here, using wheat germ agglutinin-based trans-synaptic tracing, we show that integrin 5 is selectively expressed in striatal neurons that are innervated by midbrain dopaminergic (DA) neurons from the mouse experiments. Additionally, we found that integrin 51 was activated by the administration of estradiol-2-benzoate (E2B) in striatal neurons of adult female rats. Importantly, we observed that the systemic administration of E2B into hemi-parkinsonian rat models facilitates the functional integration of grafted DA neurons derived from human induced pluripotent stem cells into the host striatal neuronal circuit via the activation of integrin 51. Finally, methamphetamine-induced abnormal rotation was recovered earlier in E2B-administrated rats than in rats that received other regimens. Our results suggest that the simultaneous administration of E2B with stem cell-derived DA progenitors can enhance the efficacy of cell transplantation therapy for PD.
Estradiol Facilitates Functional Integration of iPSC-Derived Dopaminergic Neurons into Striatal Neuronal Circuits via Activation of Integrin α5β1.
Specimen part
View SamplesMotor-related areas of neocortex are highly differentiated into several subareas from both functional and cytoarchitectural aspects in the higher primates. To assess the molecular basis of such areal specialization, we investigated the gene expression profiles of primary motor area (M1), premotor area (dorsal and ventral) (PMd and PMv) and prefrontal area (A46) in the rhesus monkey by DNA microarray method. We found that 476 genes were differentially expressed among those areas. More than half of those genes were most abundantly expressed in M1, and most genes were complementarily expressed between M1 and A46. The expression profiles of PMd and PMv were similar to each other compared to those of M1 and A46. The data will give us a fundamental basis for further analysis of structure-function relationship of the primate brain.
Differentially expressed genes among motor and prefrontal areas of macaque neocortex.
Sex
View SamplesInduced pluripotent stem cells (iPSCs) are a promising source for cell-based therapy to treat Parkinson's disease (PD), in which midbrain dopaminegic (DA) neurons progressively degenerate. However, long-term analysis of human iPSC-derived DA neurons in primate PD models has never been performed. Here we show that DA progenitor cells derived from iPSCs of both healthy individuals and PD patients survived well in the brains of PD model primates and improved animal behavior. Magnetic resonance and positron emission tomography were useful to monitor the survival and function of the DA neurons. Score-based and video-recording analyses revealed an increase in spontaneous movement of the monkeys after transplantation. Histological studies showed that the mature DA neurons extended dense neurites into the host striatum. In addition, we never observed tumor formation for two years. Thus, this preclinical study using primate models indicates that human iPSC-derived DA progenitors are clinically applicable to treat PD patients.
Human iPS cell-derived dopaminergic neurons function in a primate Parkinson's disease model.
Specimen part
View SamplesCellular dedifferentiation signifies the withdrawal of cells from a specific differentiated state into a stem cell-like undifferentiated state. However, the mechanism of dedifferentiation remains obscure. We showed that mature adipocytes (MA) and follicular granulosa cells (GC), which have distinct functions in vivo, can dedifferentiate during culture in vitro and acquire multipotency.
Gene expression profiling in multipotent DFAT cells derived from mature adipocytes.
Specimen part
View SamplesAnterior interpositus nucleus (AIN) is a proposed site of memory formation of eyeblink conditioning. A large part of the underlying molecular events, however, remains unknown. To elucidate molecular mechanisms, we examined transcriptional changes in the AIN of mice trained with delayed-type eyeblink conditioning
Molecular evidence for two-stage learning and partial laterality in eyeblink conditioning of mice.
Sex, Specimen part
View SamplesXPA is required for Nucleotide Excision Repair system, which could function to repair DNA damage induced by the UV. UV damage on the genomic DNA cannot be removed, thus persistence of damage could affect the transcriptional machinary.
Mitotic genes are transcriptionally upregulated in the fibroblast irradiated with very low doses of UV-C.
Specimen part, Disease
View SamplesDorsomorphin is a small molecule inhibitor of type I bone morphogenic protein receptors (BMPRs). We have found that dorsomorphin affects a wide range of T cell function. In order to obtain the bigger picture of the effects of DM in T cell activation. transcriptomic analysis was performed using mouse primary CD25-CD4+ T cells with either DM (4 M) or vehicle in the presence or absence of stimulation by anti-CD3 and -CD28 antibodies.
Differential effects of inhibition of bone morphogenic protein (BMP) signalling on T-cell activation and differentiation.
Specimen part, Treatment
View SamplesAnterior interpositus nucleus (AIN) is a proposed site of memory formation of eyeblink conditioning. A large part of the underlying molecular events, however, remains unknown. To elucidate molecular mechanisms, we examined transcriptional changes in the AIN of mice trained with delayed-type eyeblink conditioning
Molecular evidence for two-stage learning and partial laterality in eyeblink conditioning of mice.
Sex, Specimen part
View SamplesAnterior interpositus nucleus (AIN) is a proposed site of memory formation of eyeblink conditioning. A large part of the underlying molecular events, however, remains unknown. To elucidate molecular mechanisms, we examined transcriptional changes in the AIN of mice trained with delayed-type eyeblink conditioning
Molecular evidence for two-stage learning and partial laterality in eyeblink conditioning of mice.
Sex, Specimen part
View SamplesCellular dedifferentiation signifies the withdrawal of cells from a specific differentiated state into a stem cell-like undifferentiated state. However, the mechanism of dedifferentiation remains obscure. We showed that follicular granulosa cells (GC), which have distinct functions in vivo, can dedifferentiate during culture in vitro and acquire multipotency.
Dedifferentiated follicular granulosa cells derived from pig ovary can transdifferentiate into osteoblasts.
Specimen part
View Samples