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Open Access Publications from the University of California

Scholarly Works (14 results)

  • Thesis
  • Peer Reviewed
UC San Francisco Electronic Theses and Dissertations (2022)

The human cerebral cortex is composed of a vast diversity of neuronal and glial cell types. Decades of work in animal models has informed a model of cortical development where neural stem cells that reside along the lateral ventricle first give rise to excitatory neurons followed by glial cell types including astrocytes and oligodendrocytes, while inhibitory cortical interneurons are born outside of the cortex and migrate in. However, it remains unclear to what degree human cortical development follows this canonical model. Recent work has demonstrated that during midgestation in humans this canonical population of ventricular radial glia differentiates into truncated radial glia that remain along the ventricle in the ventricular zone (VZ), and outer radial glia that form a second stem cell niche in the outer subventricular zone (OSVZ). In this thesis, I first use fate mapping of progenitors in the human VZ and OSVZ to demonstrate that these two stem cell niches give rise to spatially and morphologically distinct populations of astrocytes, and then use Patch-seq single cell analysis to identify unique molecular markers of these astrocyte subtypes. Second, I use a novel high throughput lineage tracing tool in combination with single cell RNA-sequencing to demonstrate that human cortical neural stem cells can give rise to both excitatory neurons and inhibitory cortical interneurons, and that these two cell types can be derived from the same individual stem cell. Together this work revolutionizes our understanding of both human cortical neurogenesis and gliogenesis and provides a foundation for understanding how these unique features of human cortical development may be perturbed in disease.

    Cover page: Fate mapping of human cerebral cortex progenitors reveals novel patterns of neuronal and glial differentiation
    • Article
    • Peer Reviewed
    Recent Work (2010)
    In the United States, the older adult community is forecast to more than double by 2030. Research is needed to address their increasing mobility needs and perceived public transit barriers. In this paper, researchers evaluate the effectiveness of the Rossmoor Senior AdultCommunity transit training class (Walnut Creek, California). In Summer 2007, surveys were implemented before-and-after transit training sessions to assess changes in attitudes and intended transit behaviors. Surveys also were administered to participants who had taken the trainingcourse over the past two years to identify any longer-term changes in public transit use (longitudinal survey). Results of the ‘before-and-after” survey revealed a positive shift in participant comfort levels in taking public transportation and increased confidence in locating transit information. The majority of respondents (85.7%) stated that they planned to take transit more frequently after training. Longitudinal survey results revealed a significant decrease in private auto use as their primary transportation mode after training. Bus and transit information resource use increased significantly after training. Results from both study populations indicate that training may have an immediate impact on attitudes towards public transit and resulted in longer-term travel behavioral changes.
      Cover page: Public Transit Training: A Mechanism to Increase Ridership among Older Adults
      • Article
      • Peer Reviewed
      Working Papers (2008)

      In the United States, the older adult community is forecast to more than double by 2030. Research is needed to address their increasing mobility needs and perceived public transit barriers. In this paper, researchers evaluate the effectiveness of the Rossmoor Senior Adult Community transit training class (Walnut Creek, California). In Summer 2007, surveys were implemented before-and-after transit training sessions to assess changes in attitudes and intended transit behaviors. Surveys also were administered to participants who had taken the training course over the past two years to identify any longer-term changes in public transit use (longitudinal survey). Results of the 'before-and-after" survey revealed a positive shift in participant comfort levels in taking public transportation and increased confidence in locating transit information. The majority of respondents (85.7%) stated that they planned to take transit more frequently after training. Longitudinal survey results revealed a significant decrease in private auto use as their primary transportation mode after training. Bus and transit information resource use increased significantly after training. Results from both study populations indicate that training may have an immediate impact on attitudes towards public transit and resulted in longer-term travel behavioral changes.

        Cover page: Public Transit Training: A Mechanism to Increase Ridership Among Older Adults
        • Article
        • Peer Reviewed
        Recent Work (2009)

        Continuing its role as a leader in air pollution policymaking, California led the nation by passing the first global warming legislation in the U.S.: the Global Warming Solutions Act or Assembly Bill 32 (AB 32). The legislation requires California to decrease greenhouse gas (GHG) emissions to 1990 levels by 2020 (approximately a 27 percent reduction) using an enforceable statewide target to be phased in beginning in 2012. In addition, in 2005 Governor Schwarzenegger issued Executive Order S-3-05, which charges California with the task of reducing GHG emissions to 2000 levels by 2010, reducing emissions to 1990 levels by 2020, and reducing emissions to 80 percent below 1990 levels by 2050. This report represents a body of work conducted to assist the State of California in its efforts to develop a plan to achieve the emission targets set forth by AB 32. This research includes a literature review, expert interviews, and regional stakeholder workshops to identify and explore possible policy processes (e.g., cap and trade, budgets, feebates, etc.), mechanisms (e.g., smart growth and ITS), and strategies that could be employed to meet AB 32's GHG reduction goals.

          Cover page: Achieving California’s Land Use and Transportation Greenhouse Gas Emission Targets Under AB 32: An Exploration of Potential Policy Processes and Mechanisms
          • Article
          Research Reports (2010)
          California is home to major international ports in Long Beach, Los Angeles, and Oakland, as well as the second largest border crossing between Mexico and the U.S. California’s highways are critical commercial links from these ports of entry to the nation and carry more commercial vehicle truck traffic than any other state in the U.S. Given the high volume of truck travel in California, it is not surprising that there is a serious shortage of truck parking in the state. This shortage negatively impacts economic productivity, roadway safety, air quality, and public health. This report begins with a summary of the relevant legislation history on truck parking in the U.S. Next, the shortage of truck parking in California and its impact on congestion, safety, air quality, public health, and the trucking industry’s productivity is presented. A summary of lessons learned, from stakeholder interviews, recent surveys of truck drivers, and parking guidance information for autos, are presented next. This is followed by an evaluation of alternatives to address the truck parking problem in California, including expanded capacity, improved information, and installation of anti-idling technology. Finally, the federally funded Truck Parking Initiative in California is described. The study concludes with a summary of key findings.
            Cover page: Commercial Vehicle Parking in California: Exploratory Evaluation of the Problem and Solutions
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2017)
            Reelin is a regulator of cell migration in the nervous system, and has other functions in the development of a number of non-neuronal tissues. In addition, alterations in reelin expression levels have been reported in breast, pancreatic, liver, gastric, and other cancers. Reelin is normally expressed in mammary gland stromal cells, but whether stromal reelin contributes to breast cancer progression is unknown. Herein, we used a syngeneic mouse mammary tumor transplantation model to examine the impact of host-derived reelin on breast cancer progression. We found that transplanted syngeneic tumors grew more slowly in reelin-deficient (rl Orl -/- ) mice and had delayed metastatic colonization of the lungs. Immunohistochemistry of primary tumors revealed that tumors grown in rl Orl -/- animals had fewer blood vessels and increased macrophage infiltration. Gene expression studies from tumor tissues indicate that loss of host-derived reelin alters the balance of M1- and M2-associated macrophage markers, suggesting that reelin may influence the polarization of these cells. Consistent with this, rl Orl -/- M1-polarized bone marrow-derived macrophages have heightened levels of the M1-associated cytokines iNOS and IL-6. Based on these observations, we propose a novel function for the reelin protein in breast cancer progression.
              Cover page: Reelin Deficiency Delays Mammary Tumor Growth and Metastatic Progression
              • Article
              • Peer Reviewed
              UC San Francisco Previously Published Works (2022)
              Progenitors of the developing human neocortex reside in the ventricular and outer subventricular zones (VZ and OSVZ, respectively). However, whether cells derived from these niches have similar developmental fates is unknown. By performing fate mapping in primary human tissue, we demonstrate that astrocytes derived from these niches populate anatomically distinct layers. Cortical plate astrocytes emerge from VZ progenitors and proliferate locally, while putative white matter astrocytes are morphologically heterogeneous and emerge from both VZ and OSVZ progenitors. Furthermore, via single-cell sequencing of morphologically defined astrocyte subtypes using Patch-seq, we identify molecular distinctions between VZ-derived cortical plate astrocytes and OSVZ-derived white matter astrocytes that persist into adulthood. Together, our study highlights a complex role for cell lineage in the diversification of human neocortical astrocytes.
                Cover page: Fate mapping of neural stem cell niches reveals distinct origins of human cortical astrocytes
                • Article
                • Peer Reviewed
                UC San Francisco Previously Published Works (2020)
                The cerebrovasculature is essential to brain health and is tasked with ensuring adequate delivery of oxygen and metabolic precursors to ensure normal neurologic function. This is coordinated through a dynamic, multi-directional cellular interplay between vascular, neuronal, and glial cells. Molecular exchanges across the blood-brain barrier or the close matching of regional blood flow with brain activation are not uniformly assigned to arteries, capillaries, and veins. Evidence has supported functional segmentation of the brain vasculature. This is achieved in part through morphologic or transcriptional heterogeneity of brain vascular cells-including endothelium, pericytes, and vascular smooth muscle. Advances with single cell genomic technologies have shown increasing cell complexity of the brain vasculature identifying previously unknown cell types and further subclassifying transcriptional diversity in cardinal vascular cell types. Cell-type specific molecular transitions or zonations have been identified. In this review, we summarize emerging evidence for the expanding vascular cell diversity in the brain and how this may provide a cellular basis for functional segmentation along the arterial-venous axis.
                  Cover page: The Expanding Cell Diversity of the Brain Vasculature.Creative Commons 'BY' version 4.0 license
                  • Article
                  Research Reports (2008)
                  This report documents a review of the literature for commercial motor vehicle inspection and compliance stations and its relationship with the growth of truck travel over the next 25 years and the lack of concurrent capacity increases in staffing at such stations. Problems result in that more commercial vehicles will need to stop for inspection with longer queues at weigh stations associated with increased congestion, increased wait times, more idling trucks, and increased safety hazards. Alternatively, without stopping at inspection and compliance stations other problems will result such as roadway pavement and structure damage, and safety-related and security-related issues. Proposed advanced technological solutions to these problems are examined focusing on the four areas of pavement damage, safety, air quality, and security.
                    Cover page: Interim Report: Compliance and Commercial Vehicle Operators – A Systems Evaluation of the Problem and Virtual Solutions
                    • Article
                    • Peer Reviewed
                    UC San Francisco Previously Published Works (2022)
                    The cerebral cortex is a cellularly complex structure comprising a rich diversity of neuronal and glial cell types. Cortical neurons can be broadly categorized into two classes-excitatory neurons that use the neurotransmitter glutamate, and inhibitory interneurons that use γ-aminobutyric acid (GABA). Previous developmental studies in rodents have led to a prevailing model in which excitatory neurons are born from progenitors located in the cortex, whereas cortical interneurons are born from a separate population of progenitors located outside the developing cortex in the ganglionic eminences1-5. However, the developmental potential of human cortical progenitors has not been thoroughly explored. Here we show that, in addition to excitatory neurons and glia, human cortical progenitors are also capable of producing GABAergic neurons with the transcriptional characteristics and morphologies of cortical interneurons. By developing a cellular barcoding tool called 'single-cell-RNA-sequencing-compatible tracer for identifying clonal relationships' (STICR), we were able to carry out clonal lineage tracing of 1,912 primary human cortical progenitors from six specimens, and to capture both the transcriptional identities and the clonal relationships of their progeny. A subpopulation of cortically born GABAergic neurons was transcriptionally similar to cortical interneurons born from the caudal ganglionic eminence, and these cells were frequently related to excitatory neurons and glia. Our results show that individual human cortical progenitors can generate both excitatory neurons and cortical interneurons, providing a new framework for understanding the origins of neuronal diversity in the human cortex.
                      Cover page: Individual human cortical progenitors can produce excitatory and inhibitory neurons
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