UCSC Shared Stem Cell Facility

Since the completion of the UCSC CIRM Shared Stem Cell Facility (SSCF), we have made great strides in building an interdisciplinary stem cell research program addressing fundamental issues in stem cell biology – the genomic, molecular and cellular mechanisms regulating stem cell self-renewal and differentiation. Our contributions to stem cell research fall into two broad categories – (1) the basic biology governing stem cell identity, behavior, ability to self renew and contribute to development, and (2) the biology of multipotent stem cells committed to following specific developmental fate pathways. In this report we highlight the work of developmental biologists who are taking varied approaches to understand the mechanisms that govern specification and maintenance of stem cell identity , and to delineate the earliest steps towards forming an embryo. We also highlight investigators who study genetic, molecular and cellular factors that govern decisions of multipotent precursor cells to progress along specific cell fate pathways to form key tissues and organs, such as breast, muscle and the nervous, hematopoietic and immune systems. The research opportunities provided by the SSCF have allowed us to attract new stem cell faculty to campus, assisted the pursuit of stem cell-related research avenues by established faculty, and enabled significant progress in areas that are vital to furthering the field of regenerative medicine. This progress has been possible due to two factors: the unique design of the SSCF, with separate areas for cell culture, analysis, microscopy and teaching, all maintained to provide state-of-the-art equipment in clean, safe, highly functional workspaces; and the exceptional full-time staff that have been hired. Their combined skills, experience, knowledge, and dedication ensure that each core within the facility is operating efficiently, optimally and in compliance with all regulatory requirements. With the facility and staff now established, we are turning our attention to the next set of priorities, which include organizing user group meetings, training workshops, classes, and seminars; writing and submitting equipment grant proposals; and moving towards long-term financial stability through judicious implementation of a recharge system and other mechanisms. We have met or exceeded many of our original goals. We have brought new faculty to UCSC whose primary research focus is on stem cells, we have involved the existing faculty in stem cell research and we are training a new generation of stem cell biologists through our teaching and training efforts. In the past year, the facility also purchased 96% of our goods and services from California suppliers, exceeding the CIRM target level of 50%. In sum, with our new facility, UCSC has become one of the California Institutions making stem cell-based therapies a reality.

Since the completion of the UCSC CIRM Shared Stem Cell Facility (SSCF), UCSC continues to make great strides in building an exceptional interdisciplinary stem cell research program addressing fundamental issues in stem cell biology , focusing on the genomic, molecular and cellular mechanisms regulating stem cell self-renewal and differentiation. UCSC’s contributions to stem cell research fall into two broad categories – (1) the basic biology governing stem cell identity, behavior, ability to self renew, and contribution to development, and (2) the biology of multipotent stem cells committed to following specific developmental fate pathways. In this report we highlight the work of developmental biologists who are taking varied approaches to understand the mechanisms that govern specification and maintenance of stem cell identity, and to delineate the earliest steps towards forming an embryo. We also highlight investigators who study genetic, molecular and cellular factors that govern decisions of multipotent precursor cells to progress along specific cell fate pathways to form key tissues and organs, such as breast, muscle and the nervous, hematopoietic and immune systems. This year, UCSC labs moved from model organism to human stem cells, delved into induced pluripotent stem cells, started transplantation studies, published their work, and made additional progress toward the goals of their stem cell projects. The research opportunities provided by the SSCF have allowed UCSC’s newer stem cell faculty to establish competitive research programs and enabled existing faculty to pursue their stem cell research goals. As a result, UCSC laboratories are making significant progress in areas that are vital to furthering the goals of CIRM and the field of regenerative medicine. For example, Prof. Bin Chen has successfully differentiated hESCs into cortical neurons in culture, transplanted into neonatal mice and observed their axons extending into the spinal cord. Prof. Camilla Forsberg is making great progress in understanding the molecular changes in leukemia-initiating hematopoietic stem cells, and Prof. Lindsay Hinck is discovering important molecular pathways involved in the transition of mammary stem cells to breast cancer. This progress has been achieved because of the opportunities afforded by our CIRM shared facility, which is successful due to two primary factors: it’s unique design, with separate areas for cell culture, cytometry, microscopy, analysis and teaching, all maintained to provide state-of-the-art equipment in clean, safe, highly functional workspaces; and the exceptional full-time staff that have been hired. Their combined skills, experience, knowledge, and dedication ensure that each core within the facility is operating efficiently, optimally and in compliance with all regulatory requirements. In addition, in the past year, the facility purchased over 64% of our goods and services from California suppliers, exceeding the CIRM target level of 50%. In sum, with the SSCF, UCSC has become one of the California Institutions making stem cell-based therapies a reality.

UCSC continues to make great strides in building an exceptional interdisciplinary stem cell research program addressing fundamental issues in stem cell biology, focusing on the genomic, molecular and cellular mechanisms regulating stem cell self-renewal and differentiation. This year the UCSC CIRM Shared Stem Cell Facility (SSCF) supported research advances that lead to 9 publications (and one recently submitted), two new human iPS cell lines, a patent application, collaboration with the biotech industry, and multiple grant proposals. The research opportunities provided by the SSCF have allowed our newer stem cell faculty to establish competitive research programs, and existing faculty to pursue their stem cell goals. As a result, UCSC laboratories are making significant progress in areas that are vital to furthering the goals of CIRM and the field of regenerative medicine. UCSC’s contributions to stem cell research fall into three broad categories – (1) the basic biology governing stem cell identity, behavior, ability to self renew, and contribution to development, (2) the biology of multipotent stem cells committed to following specific developmental fate pathways, and (3) the development of tools and technologies for facilitating stem cell research. In this report we highlight the work of developmental biologists who are taking varied approaches to understand the mechanisms that govern specification and maintenance of stem cell identity, and to delineate the earliest steps towards forming an embryo. We also highlight investigators who study genetic, molecular and cellular factors that govern decisions of multipotent precursor cells to progress along specific cell fate pathways to form key tissues and organs, such as breast, muscle and the nervous, hematopoietic and immune systems. Finally we highlight the efforts of biologist working together with engineers and the R&D industry to create new instruments for advancing stem cell research. This progress has been achieved because of the opportunities afforded by our CIRM shared facility, which is successful due to two primary factors: it’s unique design, with separate areas for cell culture, cytometry, microscopy, analysis and teaching, all maintained to provide state-of-the-art equipment in clean, safe, highly functional workspaces; and the exceptional full-time staff that have been hired. Their combined skills, experience, knowledge, and dedication ensure that each core within the facility is operating efficiently, optimally and in compliance with all regulatory requirements. In addition, in the past year, the facility purchased over 70% of our goods and services from California suppliers, exceeding the CIRM target level of 50%. In sum, with the SSCF, UCSC has become one of the California Institutions making stem cell-based therapies a reality.

Stem cell researchers at UC Santa Cruz continue to focus on fundamental issues in stem cell biology. This year the UCSC CIRM Shared Stem Cell Facility (SSCF) supported research advances that lead to seven publications and several additional sponsored projects. The opportunities provided by SSCF resources have allowed our stem cell faculty to operate competitive research programs focusing on the genomic, molecular, and cellular mechanisms regulating stem cell self-renewal and differentiation in areas vital to furthering the goals of CIRM and the field of regenerative medicine. UCSC’s contributions to stem cell research fall into three broad categories: (1) the basic biology governing stem cell identity, behavior, self-renewal, and early development, (2) cell fate determination in multipotent stem cells, and (3) the development of tools and technologies to facilitate stem cell research. Highlights from this report include • The role of reprogramming factors in embryogenesis • A unique response of stem cells to double-strand DNA breaks • Approaches for determining the identities and roles of chromatin regulators involved in germline status, pluripotency, and differentiation • Studies on neural stem cell differentiation, identification of transcription factors involved in retina ganglion cell development in the eye, and non-protein coding regions of the genome regulating nervous system development • Work that is defining hematopoietic differentiation pathways, cell trafficking, and engraftment • Studies on the regulation of the mammary stem cell niche, which when deregulated can lead to tumorigenesis This work has advanced because of the opportunities afforded by our CIRM shared facility, which provides the necessary space, equipment, technical support, and knowledge. The SSCF staff has combined skills, experience, knowledge, and dedication to ensure each core within the facility is operating efficiently, optimally, and in compliance with all regulatory requirements. In addition, in the past year, the facility purchased over 85% of our goods and services from California suppliers, exceeding the CIRM target level of 50%. In sum, the SSCF enables UC Santa Cruz to increase the knowledge base required to make stem-cell-based therapies a reality.

Stem cell researchers at UC Santa Cruz continue to focus on fundamental issues in stem cell biology. This year the UCSC CIRM Shared Stem Cell Facility (SSCF) supported research advances that lead to seven publications and at least 8 new sponsored projects. The opportunities provided by SSCF resources have allowed our stem cell faculty to operate competitive research programs focusing on the genomic, molecular, and cellular mechanisms regulating stem cell self-renewal and differentiation in areas vital to furthering the goals of CIRM and the field of regenerative medicine. UCSC’s contributions to stem cell research fall into three broad categories: (1) the basic biology governing stem cell identity, behavior, self-renewal, and early development, (2) cell fate determination in multipotent stem cells, and (3) the development of tools and technologies to facilitate stem cell research. Work taking place in the SSCF includes: • The role of reprogramming factors in embryogenesis • Insights into how “germline memory” works • The genes and mechanisms involves in the development of the cells that allow sight • Uncovering recent innovations in the human lineage that underlie our large and complex brain as well as aberrations leading to neurodevelopmental disease and cancer • Research to improve hematopoietic transplantation protocols • Studies on the regulation of the mammary stem cell niche, which when deregulated can lead to tumorigenesis • Studies on the relationship of circadian timing and cell fate decisions This work has advanced because of the opportunities afforded by our CIRM shared facility, which provides the necessary space, equipment, technical support, and knowledge. The SSCF staff has combined skills, experience, knowledge, and dedication to ensure each core within the facility is operating efficiently, optimally, and in compliance with all regulatory requirements. In addition, in the past year, the facility purchased over 92% of our goods and services from California suppliers, exceeding the CIRM target level of 50%. In sum, the SSCF enables UC Santa Cruz to increase the knowledge base required to make stem-cell-based therapies a reality.

Stem cell researchers at UC Santa Cruz continue to focus on fundamental issues in stem cell biology. This year the UCSC CIRM Shared Stem Cell Facility (SSCF) supported research advances that lead to seven publications and at least 4 new sponsored projects. The opportunities provided by SSCF resources have allowed our stem cell faculty to operate competitive research programs focusing on the genomic, molecular, and cellular mechanisms regulating stem cell self-renewal and differentiation in areas vital to furthering the goals of CIRM and the field of regenerative medicine. UCSC’s contributions to stem cell research fall into three broad categories: (1) the basic biology governing stem cell identity, behavior, self-renewal, and early development, (2) cell fate determination in multipotent stem cells, and (3) the development of tools and technologies to facilitate stem cell research. Work taking place in the SSCF includes: • The unique biology of stem cell division • Insights into how “germline memory” works • The genes and mechanisms involved in the development of the cells that allow sight and regulate circadian rhythms • Uncovering recent innovations in the human lineage that underlie our large and complex brain as well as aberrations leading to neurodevelopmental disease and cancer • Research to improve hematopoietic transplantation protocols • Studies on the regulation of the mammary stem cell niche, which when deregulated can lead to tumorigenesis • Studies on the relationship of circadian timing and cell fate decisions • Investigations of the molecular mechanisms underlying prostate cancer initiation This work has advanced because of the opportunities afforded by our CIRM shared facility, which provides the necessary space, equipment, technical support, and knowledge. The SSCF staff has combined skills, experience, knowledge, and dedication to ensure each core within the facility is operating efficiently, optimally, and in compliance with all regulatory requirements. In addition, in the past year, the facility purchased 98% of our goods and services from California suppliers, exceeding the CIRM target level of 50%. In sum, the SSCF enables UC Santa Cruz to help build the knowledge base required to make stem-cell-based therapies a reality.

UCSC SHARED FACILITY YEAR 7 PUBLIC SUMMARY Stem cell investigators at UC Santa Cruz focus on fundamental issues in stem cell biology. In the past year the UCSC CIRM Shared Stem Cell Facility (SSCF) supported research that led to multiple publications and new sponsored projects. The SSCF has allowed our stem cell faculty to operate competitive research programs focusing on the genomic, molecular, and cellular mechanisms regulating stem cell self-renewal and differentiation in areas vital to furthering the goals of CIRM and the field of regenerative medicine. UCSC stem cell research falls into three broad categories: (1) the basic biology governing stem cell identity, behavior, self-renewal, and early development, (2) cell fate determination in multipotent stem cells, and (3) the development of tools and technologies to facilitate stem cell research. Work that took place in the SSCF over the past year includes: • Discovering mechanisms underlying the unique biology of stem cell division, for example the role of the centralspindlin complex in dividing cells and SLIT/ROBO signaling in asymmetric stem cell division • Insights into how chromatin regulators MES-4, PRC2 and MRG-1 influence “germline memory” • Genome engineering of primordial germ cells to lay the foundation for “genomic rescue” of endangered species • Understanding mechanisms of neural stem cell and retinal ganglion cell differentiation, and the functions of certain genes in neurological disorders and perturbed visual behavior • Understanding early events in cortical neurogenesis and specifically, aberrations in ATRX, leading to neurodevelopmental diseases such as microcephaly, macrocephaly, and its role in pediatric and adult gliomas • Defining the lineage potential of hematopoietic stem and progenitor cells during normal homeostasis as well as upon transplantation • Studies on the regulation of the mammary stem cell niche, which when dysregulated can lead to tumorigenesis, and the mechanisms by which breast cancer treatments can lead to drug resistance • Studies of post-transcriptional gene regulation by IGF2BP, which is involved in embryonic development and tumor metastasis. The CIRM shared facility has provided the necessary space, equipment, technical support, and knowledge to advance this work. The SSCF staff’s combined skills, experience, knowledge, and dedication ensures that each core within the facility is operating efficiently and in compliance with all regulatory requirements. In addition, in the past year, the facility purchased 88% of our goods and services from California suppliers, exceeding the CIRM target level of 50%. In summary, the SSCF enables UC Santa Cruz to help build the knowledge base required to make stem-cell-based therapies a reality.