Integrating population genetics, stem cell biology and cellular genomics to study complex human diseases.

Autor: Farbehi N; Garvan Weizmann Center for Cellular Genomics, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.; Graduate School of Biomedical Engineering, University of New South Wales, Sydney, New South Wales, Australia.; Aligning Science Across Parkinson's Collaborative Research Network, Chevy Chase, MD, USA., Neavin DR; Garvan Weizmann Center for Cellular Genomics, Garvan Institute of Medical Research, Sydney, New South Wales, Australia., Cuomo ASE; Garvan Weizmann Center for Cellular Genomics, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.; Centre for Population Genomics, Garvan Institute of Medical Research, University of New South Wales, Sydney, New South Wales, Australia., Studer L; Aligning Science Across Parkinson's Collaborative Research Network, Chevy Chase, MD, USA.; The Center for Stem Cell Biology and Developmental Biology Program, Sloan-Kettering Institute for Cancer Research, New York, NY, USA., MacArthur DG; Centre for Population Genomics, Garvan Institute of Medical Research, University of New South Wales, Sydney, New South Wales, Australia.; Centre for Population Genomics, Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Powell JE; Garvan Weizmann Center for Cellular Genomics, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. j.powell@garvan.org.au.; Aligning Science Across Parkinson's Collaborative Research Network, Chevy Chase, MD, USA. j.powell@garvan.org.au.; UNSW Cellular Genomics Futures Institute, University of New South Wales, Sydney, New South Wales, Australia. j.powell@garvan.org.au.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2024 May; Vol. 56 (5), pp. 758-766. Date of Electronic Publication: 2024 May 13.
DOI: 10.1038/s41588-024-01731-9
Abstrakt: Human pluripotent stem (hPS) cells can, in theory, be differentiated into any cell type, making them a powerful in vitro model for human biology. Recent technological advances have facilitated large-scale hPS cell studies that allow investigation of the genetic regulation of molecular phenotypes and their contribution to high-order phenotypes such as human disease. Integrating hPS cells with single-cell sequencing makes identifying context-dependent genetic effects during cell development or upon experimental manipulation possible. Here we discuss how the intersection of stem cell biology, population genetics and cellular genomics can help resolve the functional consequences of human genetic variation. We examine the critical challenges of integrating these fields and approaches to scaling them cost-effectively and practically. We highlight two areas of human biology that can particularly benefit from population-scale hPS cell studies, elucidating mechanisms underlying complex disease risk loci and evaluating relationships between common genetic variation and pharmacotherapeutic phenotypes.
(© 2024. Springer Nature America, Inc.)
Databáze: MEDLINE
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