Multipotent stem cells and more developmentally restricted precursors have previously been isolated from the developing nervous system, and their properties analyzed by culture assays in vitro and by transplantation in vivo. My laboratory has continued its analysis of embryonic stem cells and the factors regulating their differentiation into neurons, astrocytes and oligodendrocytes. Our current work is split between studying neural stem and progenitor cells, growing and characterizing human and mouse ES cells and developing new tools to study these cell populations. Our focus on ES cells is based on the realization that translating our findings to the clinical arena will require developing a reliable and reproducible source of cells. Our work on neural stem and progenitor cells is focused on identifying novel genes or novel roles of known genes, that may regulate the developmental process and extending the analysis of the behavior of stem cells in adult models of injury and disease. A long-term plan is to develop rat transgenic models, rat ES cell lines, and in-utero transplant paradigms. Recent results include a) Demonstrating neural differentiation of human ES (embryonic stem) cells b) Demonstrating a role for Nkx2.2 (Homeodomain protein) and ngn-3 (neurogenin-3) in regulating oligodendrocye differentiation c) Showing that Hes-1 (enhancer of split homologue), Hes-5 and BMP?s (Bone morphogenetic protein) regulate astrocyte differentiation from glial progenitor cells d) Identifying markers for neural stem cells e) Developing a stem cell microarray f) Generating a transgenic rat . Our more recent focus on human ES cells has lead to the development of feeder free culture conditions for ES cells, the establishment fo a database of ES and EB specific markers and the development of protocols for dopaminergic differentiation of cells. Together these results provide a strong basis for understanding how stem and precursor cell differentiation is regulated. Our model of differentiation suggests a sequential acquisition of differentiation markers. Our future work will focus on extending these observations and understanding how stem cells age. Some recent publications related to this work are listed below .

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Intramural Research (Z01)
Project #
1Z01AG000324-03
Application #
6969257
Study Section
(LNS)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2004
Total Cost
Indirect Cost
Name
Aging
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Schwartz, Catherine M; Tavakoli, Tahereh; Jamias, Charmaine et al. (2012) Stromal factors SDF1*, sFRP1, and VEGFD induce dopaminergic neuron differentiation of human pluripotent stem cells. J Neurosci Res 90:1367-81
Sun, Yu; Li, Huai; Liu, Ying et al. (2007) Cross-species transcriptional profiles establish a functional portrait of embryonic stem cells. Genomics 89:22-35
Liu, Ying; Shin, Soojung; Zeng, Xianmin et al. (2006) Genome wide profiling of human embryonic stem cells (hESCs), their derivatives and embryonal carcinoma cells to develop base profiles of U.S. Federal government approved hESC lines. BMC Dev Biol 6:20
Cai, Jingli; Shin, Soojung; Wright, Lynda et al. (2006) Massively parallel signature sequencing profiling of fetal human neural precursor cells. Stem Cells Dev 15:232-44
Luo, Yongquan; Cai, Jingli; Xue, Haipeng et al. (2006) SDF1alpha/CXCR4 signaling stimulates beta-catenin transcriptional activity in rat neural progenitors. Neurosci Lett 398:291-5
Zhang, Peisu; Furukawa, Katsutoshi; Opresko, Patricia L et al. (2006) TRF2 dysfunction elicits DNA damage responses associated with senescence in proliferating neural cells and differentiation of neurons. J Neurochem 97:567-81
Li, Huai; Liu, Ying; Shin, Soojung et al. (2006) Transcriptome coexpression map of human embryonic stem cells. BMC Genomics 7:103
Yang, Amy X; Mejido, Josef; Luo, Yongquan et al. (2005) Development of a focused microarray to assess human embryonic stem cell differentiation. Stem Cells Dev 14:270-84
Magnus, T; Rao, M S (2005) Neural stem cells in inflammatory CNS diseases: mechanisms and therapy. J Cell Mol Med 9:303-19
Lepore, Angelo C; Bakshi, Ajay; Swanger, Sharon A et al. (2005) Neural precursor cells can be delivered into the injured cervical spinal cord by intrathecal injection at the lumbar cord. Brain Res 1045:206-16

Showing the most recent 10 out of 41 publications