Molecular signature and functional properties of human pluripotent stem cell-derived brain pericytes
Molecular signature and functional properties of human pluripotent stem cell-derived brain pericytes
Abstract Brain pericytes maintain blood-brain barrier (BBB), secrete neurotrophic factors and clear toxic proteins. Their loss in neurological disorders leads to BBB breakdown, neuronal dysfunction, and cognitive decline. Therefore, cell therapy to replace lost pericytes holds potential to restore impaired cerebrovascular and brain functions. Here, we show by a quantitative analysis of 8,344 proteins and 20,572 phosphopeptides that human iPSC-derived brain pericytes (iPSC-PC) share 96% of total proteins and 98% of protein phosphorylation sites with primary human brain pericytes. This includes cell adhesion and tight junction proteins, transcription factors, and different protein kinase families of the human kinome. In pericyte-deficient mice, iPSC-PC home to host brain capillaries to form hybrid human-mouse microvessels. They repair BBB leaks and protect against neuron loss, which we show requires PDGRFB and pleiotrophin. They also clear Alzheimer’s amyloid-β and tau neurotoxins via lipoprotein receptor. Thus, iPSC-PC may offer a valuable replacement therapy for pericyte-deficient neurological disorders.
Zlokovic Berislav V.、Nelson Amy R.、Bosworth Allison、Chakhoyan Ararat、Wang Yaoming、Rust Ruslan、Griffin Casey、Sagare Abhay P.、Coba Marcelo、Montagne Axel、Clementel Veronica、Kisler Kassandra、TCW Julia
Department of Physiology and Neuroscience, University of Southern California||Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern CaliforniaDepartment of Physiology and Neuroscience, University of Southern California||Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California||Department of Physiology and Cell Biology, University of South AlabamaDepartment of Physiology and Neuroscience, University of Southern California||Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern CaliforniaDepartment of Physiology and Neuroscience, University of Southern California||Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern CaliforniaDepartment of Physiology and Neuroscience, University of Southern California||Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern CaliforniaDepartment of Physiology and Neuroscience, University of Southern California||Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California||Institute for Regenerative Medicine (IREM), University of Zurich, Campus SchlierenEli and Edythe Broad Center for Regenerative Medicine, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California||Department of Molecular Pathobiology, New York UniversityDepartment of Physiology and Neuroscience, University of Southern California||Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern CaliforniaDepartment of Physiology and Neuroscience, University of Southern California||Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California||Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern CaliforniaDepartment of Physiology and Neuroscience, University of Southern California||Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California||UK Dementia Research Institute at the University of Edinburgh, Centre for Clinical Brain Sciences, Chancellor?ˉs Building, Edinburgh Medical SchoolDepartment of Physiology and Neuroscience, University of Southern California||Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California||Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern CaliforniaDepartment of Physiology and Neuroscience, University of Southern California||Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern CaliforniaDepartment of Pharmacology, Physiology & Biophysics, Chobanian & Avedisian School of Medicine, Boston University
神经病学、精神病学基础医学分子生物学
Zlokovic Berislav V.,Nelson Amy R.,Bosworth Allison,Chakhoyan Ararat,Wang Yaoming,Rust Ruslan,Griffin Casey,Sagare Abhay P.,Coba Marcelo,Montagne Axel,Clementel Veronica,Kisler Kassandra,TCW Julia.Molecular signature and functional properties of human pluripotent stem cell-derived brain pericytes[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2023.06.26.546577.点此复制
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