title: GSK3β Inhibition Promotes Efficient Myeloid and Lymphoid Hematopoiesis from Non-human Primate-Induced Pluripotent Stem Cells.
abstract: Advances in the scalable production of blood cells from induced pluripotent stem cells (iPSCs) open prospects for the clinical translation of de novo generated blood products, and evoke the need for preclinical evaluation of their efficacy, safety, and immunogenicity in large animal models. Due to substantial similarities with humans, the outcomes of cellular therapies in non-human primate (NHP) models can be readily extrapolated to a clinical setting. However, the use of this model is hampered by relatively low efficiency of blood generation and lack of lymphoid potential in NHP-iPSC differentiation cultures. Here, we generated transgene-free iPSCs from different NHP species and showed the efficient induction of mesoderm, myeloid, and lymphoid cells from these iPSCs using a GSK3β inhibitor. Overall, our studies enable scalable production of hematopoietic progenitors from NHP-iPSCs, and lay the foundation for preclinical testing of iPSC-based therapies for blood and immune system diseases in an NHP model.
authors.affiliation: National Primate Research Center, University of Wisconsin, 1220 Capitol Court, Madison, WI 53715, USA.
authors.forename: Saritha S
authors.initials: SS
authors.lastname: D'Souza
authors.affiliation: National Primate Research Center, University of Wisconsin, 1220 Capitol Court, Madison, WI 53715, USA.
authors.forename: John
authors.initials: J
authors.lastname: Maufort
authors.affiliation: National Primate Research Center, University of Wisconsin, 1220 Capitol Court, Madison, WI 53715, USA.
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Morgridge Institute for Research, 309 North Orchard Street, Madison, WI 53715, USA.
authors.forename: Jiuchun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Morgridge Institute for Research, 309 North Orchard Street, Madison, WI 53715, USA.
authors.forename: Kimberley
authors.initials: K
authors.lastname: Smuga-Otto
authors.affiliation: Morgridge Institute for Research, 309 North Orchard Street, Madison, WI 53715, USA; Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53707, USA; Department of Molecular, Cellular & Developmental Biology, University of California, Santa Barbara, CA 93106, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Thomson
authors.affiliation: National Primate Research Center, University of Wisconsin, 1220 Capitol Court, Madison, WI 53715, USA; Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53707, USA; Department of Pathology and Laboratory Medicine, University of Wisconsin, 1685 Highland Avenue, Madison WI 53705, USA. Electronic address: islukvin@wisc.edu.
authors.forename: Igor I
authors.initials: II
authors.lastname: Slukvin
mesh_terms: D000818:Animals; D002460:Cell Line; D019070:Cell Lineage / Q000187:drug effects; D018920:Coculture Techniques; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology* / Q000187:drug effects; D011323:Primates; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3