title: Gene profiling of human induced pluripotent stem cell-derived astrocyte progenitors following spinal cord engraftment.
abstract: The generation of human induced pluripotent stem cells (hiPSCs) represents an exciting advancement with promise for stem cell transplantation therapies as well as for neurological disease modeling. Based on the emerging roles for astrocytes in neurological disorders, we investigated whether hiPSC-derived astrocyte progenitors could be engrafted to the rodent spinal cord and how the characteristics of these cells changed between in vitro culture and after transplantation to the in vivo spinal cord environment. Our results show that human embryonic stem cell- and hiPSC-derived astrocyte progenitors survive long-term after spinal cord engraftment and differentiate to astrocytes in vivo with few cells from other lineages present. Gene profiling of the transplanted cells demonstrates the astrocyte progenitors continue to mature in vivo and upregulate a variety of astrocyte-specific genes. Given this mature astrocyte gene profile, this work highlights hiPSCs as a tool to investigate disease-related astrocyte biology using in vivo disease modeling with significant implications for human neurological diseases currently lacking animal models.
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Departments of Rehabilitation and Regenerative Medicine, Pathology and Cell Biology, Neurology, and Neuroscience, Center for Motor Neuron Biology and Disease, Columbia Stem Cell Initiative, Columbia University Medical Center, New York, New York, Stem Cell Laboratory for CNS Disease Modeling-MultiPark, Department of Experimental Medical Science, Lund University, Lund, Sweden; Howard Hughes Medical Institute, Harvard Stem Cell Institute and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Haidet-Phillips
authors.forename: Laurent
authors.initials: L
authors.lastname: Roybon
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Gross
authors.forename: Alisha
authors.initials: A
authors.lastname: Tuteja
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Donnelly
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Richard
authors.forename: Myungsung
authors.initials: M
authors.lastname: Ko
authors.forename: Alex
authors.initials: A
authors.lastname: Sherman
authors.forename: Kevin
authors.initials: K
authors.lastname: Eggan
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Henderson
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Maragakis
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D064593:Heterografts; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism
keywords: Astrocytes; Gene profiling; Human induced pluripotent stem cells; Stem cell transplantation