title: Human induced pluripotent stem cells are capable of B-cell lymphopoiesis.
abstract: Induced pluripotent stem (iPS) cells offer a unique potential for understanding the molecular basis of disease and development. Here we have generated several human iPS cell lines, and we describe their pluripotent phenotype and ability to differentiate into erythroid cells, monocytes, and endothelial cells. More significantly, however, when these iPS cells were differentiated under conditions that promote lympho-hematopoiesis from human embryonic stem cells, we observed the formation of pre-B cells. These cells were CD45(+)CD19(+)CD10(+) and were positive for transcripts Pax5, IL7αR, λ-like, and VpreB receptor. Although they were negative for surface IgM and CD5 expression, iPS-derived CD45(+)CD19(+) cells also exhibited multiple genomic D-J(H) rearrangements, which supports a pre-B-cell identity. We therefore have been able to demonstrate, for the first time, that human iPS cells are able to undergo hematopoiesis that contributes to the B-cell lymphoid lineage.
authors.affiliation: Stem Cell Research Laboratory, National Health Service Blood and Transplant, John Radcliffe Hospital, Oxford, UK. lee.carpenter@nhsbt.nhs.uk
authors.forename: Lee
authors.initials: L
authors.lastname: Carpenter
authors.forename: Ram
authors.initials: R
authors.lastname: Malladi
authors.forename: Cheng-Tao
authors.initials: CT
authors.lastname: Yang
authors.forename: Anna
authors.initials: A
authors.lastname: French
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Pilkington
authors.forename: Richard W
authors.initials: RW
authors.lastname: Forsey
authors.forename: Jackie
authors.initials: J
authors.lastname: Sloane-Stanley
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Silk
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Davies
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Fairchild
authors.forename: Tariq
authors.initials: T
authors.lastname: Enver
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Watt
mesh_terms: D000328:Adult; D018941:Antigens, CD19 / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology* / Q000502:physiology; D002460:Cell Line; D019070:Cell Lineage / Q000276:immunology; D006801:Humans; D054444:Immunoglobulin Light Chains, Surrogate / Q000235:genetics; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000378:metabolism; D038041:Lymphopoiesis / Q000502:physiology*; D015260:Neprilysin / Q000378:metabolism; D051757:PAX5 Transcription Factor / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology* / Q000502:physiology; D020395:Receptors, Interleukin-7 / Q000235:genetics
chemical_list: D018941:Antigens, CD19; D054444:Immunoglobulin Light Chains, Surrogate; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D020395:Receptors, Interleukin-7; C515639:VPREB1 protein, human; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human; D015260:Neprilysin