title: Bottlenecks in deriving definitive hematopoietic stem cells from human pluripotent stem cells: a CIRM mini-symposium and workshop report.
abstract: On August 29, 2013, the California Institute for Regenerative Medicine (CIRM) convened a small group of investigators in San Francisco, CA, to discuss a longstanding challenge in the stem cell field: the inability to derive fully functional, definitive hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs). To date, PSC-derived HSCs have been deficient in their developmental potential and their ability to self-renew and engraft upon transplantation. Tasked with identifying key challenges to overcoming this "HSC bottleneck", workshop participants identified critical knowledge gaps in two key areas: (a) understanding the ontogeny of human HSCs, and (b) understanding of the intrinsic and extrinsic factors that govern HSC behavior and function. They agreed that development of new methods and tools is critical for addressing these knowledge gaps. These include molecular profiling of key HSC properties, development of new model systems/assays for predicting and assessing HSC function, and novel technological advancements for manipulating cell culture conditions and genetic programs. The workshop produced tangible advances, including providing a current definition of the nature and challenge of the HSC bottleneck and identifying key mechanistic studies of HSC biology that should be prioritized for future funding initiatives (e.g., including higher risk approaches that have potential for high gain).
authors: California Institute for Regenerative Medicine, San Francisco, California, USA kshepard@cirm.ca.gov.
authors: Kelly A
authors: KA
authors: Shepard
authors: California Institute for Regenerative Medicine, San Francisco, California, USA.
authors: Sohel
authors: S
authors: Talib
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival; D018507:Gene Expression Regulation, Developmental; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D039904:Pluripotent Stem Cells / Q000378:metabolism* / Q000637:transplantation; D057905:Stem Cell Research
chemical_list: D015415:Biomarkers
keywords: Adult hematopoietic stem cells; Differentiation; Hematopoiesis; Hematopoietic stem cells; Pluripotent stem cells; Stem/progenitor cell