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Reprogramming of T Cells from Human Peripheral Blood
Yuin-Han Loh1, 2, Odelya Hartung1, 2, Hu Li3, 4, Chunguang Guo5, 6, 7, Julie M. Sahalie1, 2, Philip D. Manos1, 2, Achia Urbach1, 2, Garrett C. Heffner1, 2, Marica Grskovic8, Francois Vigneault7, M. William Lensch1, 2, 5, In-Hyun Park1, 2, Suneet Agarwal1, 2, George M. Church7, James J. Collins3, 4, 5, Stefan Irion8, , and George Q. Daley1, 2, 5, 9, 10
Stem Cell Transplantation Program, Division of Pediatric Hematology Oncology, Children's Hospital Boston and Dana-Farber Cancer Institute; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
2 Harvard Stem Cell Institute, Cambridge, MA 02138, USA
3 Department of Biomedical Engineering and Center for BioDynamics, Boston University, Boston, MA 02215, USA
4 Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA
5 Howard Hughes Medical Institute, Boston, MA 02115, USA
6 Immune Diseases Institute, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
7 Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
8 iPierian, Inc. South San Francisco, CA 94080, USA
9 Division of Hematology, Brigham and Women's Hospital, Boston, MA 02115, USA
10 Manton Center for Orphan Disease Research, Boston, MA 02115, USA
Human induced pluripotent stem cells (iPSCs) derived from somatic cells of patients hold great promise for modeling human diseases. Dermal fibroblasts are frequently used for reprogramming, but require an invasive skin biopsy and a prolonged period of expansion in cell culture prior to use. Here, we report the derivation of iPSCs from multiple human blood sources including peripheral blood mononuclear cells (PBMCs) harvested by routine venipuncture. Peripheral blood-derived human iPSC lines are comparable to human embryonic stem cells (ESCs) with respect to morphology, expression of surface antigens, activation of endogenous pluripotency genes, DNA methylation, and differentiation potential. Analysis of immunoglobulin and T cell receptor gene rearrangement revealed that some of the PBMC iPSCs were derived from T cells, documenting derivation of iPSCs from terminally differentiated cell types. Importantly, peripheral blood cells can be isolated with minimal risk to the donor and can be obtained in sufficient numbers to enable reprogramming without the need for prolonged expansion in culture. Reprogramming from blood cells thus represents a fast, safe, and efficient way of generating patient-specific iPSCs.
