Susan K Goderie

Publications (8)99.39 Total impact

• Article: The effect of long-term release of Shh from implanted biodegradable microspheres on recovery from spinal cord injury in mice.

  Natalia Lowry, Susan K Goderie, Patricia Lederman, Carol Charniga, Michael R Gooch, Kristina D Gracey, Akhilesh Banerjee, Supriya Punyani, Jerry Silver, Ravi S Kane, Jeffrey H Stern, Sally Temple
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  ABSTRACT: After spinal cord injury (SCI), loss of cells and damage to ascending and descending tracts can result in paralysis. Current treatments for SCI are based on patient stabilization, and much-needed regenerative therapies are still under development. To activate and instruct stem and progenitor cells or injured tissue to aid SCI repair, it is important to modify the injury environment for a protracted period, to allow time for cell activation, proliferation and appropriate fate differentiation. Shh plays a critical role in spinal cord formation, being involved in multiple processes: it promotes production of motor neurons and oligodendrocytes from ventral cord progenitor cells and serves as an axon guidance molecule. Hence Shh is a candidate pleiotropic beneficial environmental factor for spinal cord regeneration. Here we show that administration of biodegradable microspheres that provide sustained, controlled delivery of Shh resulted in significant functional improvement in two different mouse models of SCI: contusion and dorsal hemioversection. The mechanism is multifactorial, involving increased proliferation of endogenous NG2+ oligodendrocyte lineage cells, decreased astrocytic scar formation and increased sprouting and growth of corticospinal (CST) and raphespinal tract (RST) fibers. Thus, long-term administration of Shh is a potential valuable therapeutic intervention for SCI.
  Biomaterials 04/2012; 33(10):2892-901. · 7.40 Impact Factor
• Article: Vertebrate neural stem cell segmentation, tracking and lineaging with validation and editing.

  Mark Winter, Eric Wait, Badrinath Roysam, Susan K Goderie, Rania Ahmed Naguib Ali, Erzsebet Kokovay, Sally Temple, Andrew R Cohen
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  ABSTRACT: This protocol and the accompanying software program called LEVER (lineage editing and validation) enable quantitative automated analysis of phase-contrast time-lapse images of cultured neural stem cells. Images are captured at 5-min intervals over a period of 5-15 d as the cells proliferate and differentiate. LEVER automatically segments, tracks and generates lineage trees of the stem cells from the image sequence. In addition to generating lineage trees capturing the population dynamics of clonal development, LEVER extracts quantitative phenotypic measurements of cell location, shape, movement and size. When available, the system can include biomolecular markers imaged using fluorescence. It then displays the results to the user for highly efficient inspection and editing to correct any errors in the segmentation, tracking or lineaging. To enable high-throughput inspection, LEVER incorporates features for rapid identification of errors and for learning from user-supplied corrections to automatically identify and correct related errors.
  Nature Protocol 01/2011; 6(12):1942-52. · 8.36 Impact Factor
• Article: Adult SVZ stem cells lie in a vascular niche: a quantitative analysis of niche cell-cell interactions.

  Qin Shen, Yue Wang, Erzsebet Kokovay, Gang Lin, Shu-Mien Chuang, Susan K Goderie, Badrinath Roysam, Sally Temple
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  ABSTRACT: There is an emerging understanding of the importance of the vascular system within stem cell niches. Here, we examine whether neural stem cells (NSCs) in the adult subventricular zone (SVZ) lie close to blood vessels, using three-dimensional whole mounts, confocal microscopy, and automated computer-based image quantification. We found that the SVZ contains a rich plexus of blood vessels that snake along and within neuroblast chains. Cells expressing stem cell markers, including GFAP, and proliferation markers are closely apposed to the laminin-containing extracellular matrix (ECM) surrounding vascular endothelial cells. Apical GFAP+ cells are admixed within the ependymal layer and some span between the ventricle and blood vessels, occupying a specialized microenvironment. Adult SVZ progenitor cells express the laminin receptor alpha6beta1 integrin, and blocking this inhibits their adhesion to endothelial cells, altering their position and proliferation in vivo, indicating that it plays a functional role in binding SVZ stem cells within the vascular niche.
  Cell stem cell 10/2008; 3(3):289-300. · 23.56 Impact Factor
• Article: Multipotent embryonic spinal cord stem cells expanded by endothelial factors and Shh/RA promote functional recovery after spinal cord injury.

  Natalia Lowry, Susan K Goderie, Matthew Adamo, Patricia Lederman, Carol Charniga, Jasrai Gill, Jerry Silver, Sally Temple
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  ABSTRACT: Cell transplantation is a promising way to treat spinal cord injury and neurodegenerative disorders. Neural stem cells taken from the embryonic spinal cord are an appealing source of cells for transplantation because these cells are committed to making spinal cord progeny. However these stem cells are rare and require expansion in tissue culture to generate sufficient cells for transplantation. We have developed a novel method for expanding embryonic mouse spinal cord stem cells using a co-culture system with endothelial cells. This method improves neural stem cell survival and preserves their multipotency, including their ability to make motor neurons. Transplantation of endothelial-expanded neural stem cells that were treated with sonic hedgehog(Shh) and retinoic acid (RA) during the expansion phase, into an adult mouse SCI model resulted in significant recovery of sensory and motor function.
  Experimental Neurology 03/2008; 209(2):510-22. · 4.70 Impact Factor
• Article: Automated cell lineage construction: a rapid method to analyze clonal development established with murine neural progenitor cells.

  Omar Al-Kofahi, Richard J Radke, Susan K Goderie, Qin Shen, Sally Temple, Badrinath Roysam
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  ABSTRACT: Understanding cell lineage relationships is fundamental to understanding development, and can shed light on disease etiology and progression. We present a method for automated tracking of lineages of proliferative, migrating cells from a sequence of images. The method is applicable to image sequences gathered either in vitro or in vivo. Currently, generating lineage trees from progenitor cells over time is a tedious, manual process, which limits the number of cell measurements that can be practically analyzed. In contrast, the automated method is rapid and easily applied, and produces a wealth of measurements including the precise position, shape, cell-cell contacts, motility and ancestry of each cell in every frame, and accurate timings of critical events, e.g., mitosis and cell death. Furthermore, it automatically produces graphical output that is immediately accessible. Application to clonal development of mouse neural progenitor cells growing in cell culture reveals complex changes in cell cycle rates during neuron and glial production. The method enables a level of quantitative analysis of cell behavior over time that was previously infeasible.
  Cell cycle (Georgetown, Tex.) 03/2006; 5(3):327-35. · 5.36 Impact Factor
• Article: Stage-specific changes in gene expression in acutely isolated mouse CNS progenitor cells.

  Natalia Abramova, Carol Charniga, Susan K Goderie, Sally Temple
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  ABSTRACT: Neural progenitor cells can be derived from a variety of developmental stages when they are preferentially proliferating, undergoing neurogenesis or undergoing gliogenesis. We used FACS sorting and the LeX surface marker to enrich neural progenitor cells from different embryonic stages and adult and compared their gene expression profiles using Affymetrix Microarrays. Our results show that, while there are common genes expressed in the progenitor cell population from all stages, there are also significant differences in gene expression patterns that correlate with stage-related behaviors. These data indicate that progenitor cells change during development and that adult and embryonic neural progenitor cells are intrinsically different.
  Developmental Biology 08/2005; 283(2):269-81. · 4.07 Impact Factor
• Article: Asymmetric distribution of EGFR receptor during mitosis generates diverse CNS progenitor cells.

  Yu Sun, Susan K Goderie, Sally Temple
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  ABSTRACT: It has been debated whether asymmetric distribution of cell surface receptors during mitosis could generate asymmetric cell divisions by yielding daughters with different environmental responsiveness and, thus, different fates. We have found that in mouse embryonic forebrain ventricular and subventricular zones, the EGFR can distribute asymmetrically during mitosis in vivo and in vitro. This occurs during divisions yielding two Nestin+ progenitor cells, via an actin-dependent mechanism. The resulting sibling progenitor cells respond differently to EGFR ligand in terms of migration and proliferation. Moreover, they express different phenotypic markers: the EGFRhigh daughter usually has radial glial/astrocytic markers, while its EGFRlow sister lacks them, indicating fate divergence. Lineage trees of cultured cortical glioblasts reveal repeated EGFR asymmetric distribution, and asymmetric divisions underlie formation of oligodendrocytes and astrocytes in clones. These data suggest that asymmetric EGFR distribution contributes to forebrain development by creating progenitors with different proliferative, migratory, and differentiation responses to ligand.
  Neuron 04/2005; 45(6):873-86. · 14.74 Impact Factor
• Source

  Available from: uni-frankfurt.de

  Article: Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells.

  Qin Shen, Susan K Goderie, Li Jin, Nithin Karanth, Yu Sun, Natalia Abramova, Peter Vincent, Kevin Pumiglia, Sally Temple
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  ABSTRACT: Neural stem cells are reported to lie in a vascular niche, but there is no direct evidence for a functional relationship between the stem cells and blood vessel component cells. We show that endothelial cells but not vascular smooth muscle cells release soluble factors that stimulate the self-renewal of neural stem cells, inhibit their differentiation, and enhance their neuron production. Both embryonic and adult neural stem cells respond, allowing extensive production of both projection neuron and interneuron types in vitro. Endothelial coculture stimulates neuroepithelial cell contact, activating Notch and Hes 1 to promote self-renewal. These findings identify endothelial cells as a critical component of the neural stem cell niche.
  Science 06/2004; 304(5675):1338-40. · 31.20 Impact Factor