title: A novel serum-free monolayer culture for orderly hematopoietic differentiation of human pluripotent cells via mesodermal progenitors.
abstract: Elucidating the in vitro differentiation of human embryonic stem (ES) and induced pluripotent stem (iPS) cells is important for understanding both normal and pathological hematopoietic development in vivo. For this purpose, a robust and simple hematopoietic differentiation system that can faithfully trace in vivo hematopoiesis is necessary. In this study, we established a novel serum-free monolayer culture that can trace the in vivo hematopoietic pathway from ES/iPS cells to functional definitive blood cells via mesodermal progenitors. Stepwise tuning of exogenous cytokine cocktails induced the hematopoietic mesodermal progenitors via primitive streak cells. These progenitors were then differentiated into various cell lineages depending on the hematopoietic cytokines present. Moreover, single cell deposition assay revealed that common bipotential hemoangiogenic progenitors were induced in our culture. Our system provides a new, robust, and simple method for investigating the mechanisms of mesodermal and hematopoietic differentiation.
authors.affiliation: Clinical Application Department, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Niwa
authors.forename: Toshio
authors.initials: T
authors.lastname: Heike
authors.forename: Katsutsugu
authors.initials: K
authors.lastname: Umeda
authors.forename: Koichi
authors.initials: K
authors.lastname: Oshima
authors.forename: Itaru
authors.initials: I
authors.lastname: Kato
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sakai
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Suemori
authors.forename: Tatsutoshi
authors.initials: T
authors.lastname: Nakahata
authors.forename: Megumu K
authors.initials: MK
authors.lastname: Saito
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001773:Blood Cells / Q000166:cytology / Q000187:drug effects; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D019070:Cell Lineage / Q000187:drug effects; D002999:Clone Cells; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology* / Q000187:drug effects; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D016895:Culture Media, Serum-Free; D040301:Vascular Endothelial Growth Factor Receptor-2; D017493:Leukocyte Common Antigens