title: Tenascin C promotes hematoendothelial development and T lymphoid commitment from human pluripotent stem cells in chemically defined conditions.
abstract: The recent identification of hemogenic endothelium (HE) in human pluripotent stem cell (hPSC) cultures presents opportunities to investigate signaling pathways that are essential for blood development from endothelium and provides an exploratory platform for de novo generation of hematopoietic stem cells (HSCs). However, the use of poorly defined human or animal components limits the utility of the current differentiation systems for studying specific growth factors required for HE induction and manufacturing clinical-grade therapeutic blood cells. Here, we identified chemically defined conditions required to produce HE from hPSCs growing in Essential 8 (E8) medium and showed that Tenascin C (TenC), an extracellular matrix protein associated with HSC niches, strongly promotes HE and definitive hematopoiesis in this system. hPSCs differentiated in chemically defined conditions undergo stages of development similar to those previously described in hPSCs cocultured on OP9 feeders, including the formation of VE-Cadherin(+)CD73(-)CD235a/CD43(-) HE and hematopoietic progenitors with myeloid and T lymphoid potential.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53792, USA.
authors.forename: Gene
authors.initials: G
authors.lastname: Uenishi
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Theisen
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA.
authors.forename: Jeong-Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA.
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA.
authors.forename: Matt
authors.initials: M
authors.lastname: Raymond
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA.
authors.forename: Maxim
authors.initials: M
authors.lastname: Vodyanik
authors.affiliation: Morgridge Institute for Research, Madison, WI 53707, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Swanson
authors.affiliation: Morgridge Institute for Research, Madison, WI 53707, USA.
authors.forename: Ron
authors.initials: R
authors.lastname: Stewart
authors.affiliation: Morgridge Institute for Research, Madison, WI 53707, 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, Santa Barbara, CA 93106, USA.
authors.forename: James
authors.initials: J
authors.lastname: Thomson
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53792, USA; Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA. Electronic address: islukvin@wisc.edu.
authors.forename: Igor
authors.initials: I
authors.lastname: Slukvin
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage; D002478:Cells, Cultured; D016000:Cluster Analysis; D018920:Coculture Techniques; D003470:Culture Media; D020869:Gene Expression Profiling; D055018:Hemangioblasts / Q000166:cytology* / Q000378:metabolism; D006410:Hematopoiesis / Q000235:genetics; D006801:Humans; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology* / Q000378:metabolism; D017154:Stromal Cells; D019063:Tenascin / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome
chemical_list: D003470:Culture Media; D019063:Tenascin