Definitive proof for direct reprogramming of hematopoietic cells to pluripotency.
Generation of induced pluripotent stem cells (iPSCs) generally uses fibroblastic cells, but other cell sources may prove useful in both research and clinical settings. Although proof of cellular origin requires genetic-marker identification in both target cells and established iPSCs, somatic cells other than mature lymphocytes mostly lack such markers. Here we show definitive proof of direct reprogramming of murine hematopoietic cells with no rearranged genes. Using iPSC factor transduction, we successfully derived iPSCs from bone marrow progenitor cells obtained from a mouse whose hematopoiesis was reconstituted from a single congenic hematopoietic stem cell. Established clones were demonstrated to be genetically identical to the transplanted single hematopoietic stem cell, thus proving their cellular origin. These hematopoietic cell-derived iPSCs showed typical characteristics of iPSCs, including the ability to contribute to chimerism in mice. These results will prompt further use of hematopoietic cells for iPSC generation while enabling definitive studies to test how cellular sources influence characteristics of descendant iPSCs.
Okabe
Motohito
M
Division of Stem Cell Therapy, Center for Stem Cell and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Otsu
Makoto
M
Ahn
Dong Hyuck
DH
Kobayashi
Toshihiro
T
Morita
Yohei
Y
Wakiyama
Yukiko
Y
Onodera
Masafumi
M
Eto
Koji
K
Ema
Hideo
H
Nakauchi
Hiromitsu
H
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D019070:Cell Lineage; D005091:Exons; D006410:Hematopoiesis / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D008214:Lymphocytes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D008957:Models, Genetic; D039904:Pluripotent Stem Cells / Q000166:cytology; D020133:Reverse Transcriptase Polymerase Chain Reaction