Direct conversion of human fibroblasts to multilineage blood progenitors

Eva Szabo, Shravanti Rampalli, Ruth M. Risueño, Angelique Schnerch, Ryan Mitchell, Aline Fiebig-Comyn, Marilyne Levadoux-Martin and Mickie Bhatia ()
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Eva Szabo: Stem Cell and Cancer Research Institute, McMaster University
Shravanti Rampalli: Stem Cell and Cancer Research Institute, McMaster University
Ruth M. Risueño: Stem Cell and Cancer Research Institute, McMaster University
Angelique Schnerch: Stem Cell and Cancer Research Institute, McMaster University
Ryan Mitchell: Stem Cell and Cancer Research Institute, McMaster University
Aline Fiebig-Comyn: Stem Cell and Cancer Research Institute, McMaster University
Marilyne Levadoux-Martin: Stem Cell and Cancer Research Institute, McMaster University
Mickie Bhatia: Stem Cell and Cancer Research Institute, McMaster University

Nature, 2010, vol. 468, issue 7323, 521-526

Abstract: Abstract As is the case for embryo-derived stem cells, application of reprogrammed human induced pluripotent stem cells is limited by our understanding of lineage specification. Here we demonstrate the ability to generate progenitors and mature cells of the haematopoietic fate directly from human dermal fibroblasts without establishing pluripotency. Ectopic expression of OCT4 (also called POU5F1)-activated haematopoietic transcription factors, together with specific cytokine treatment, allowed generation of cells expressing the pan-leukocyte marker CD45. These unique fibroblast-derived cells gave rise to granulocytic, monocytic, megakaryocytic and erythroid lineages, and demonstrated in vivo engraftment capacity. We note that adult haematopoietic programs are activated, consistent with bypassing the pluripotent state to generate blood fate: this is distinct from haematopoiesis involving pluripotent stem cells, where embryonic programs are activated. These findings demonstrate restoration of multipotency from human fibroblasts, and suggest an alternative approach to cellular reprogramming for autologous cell-replacement therapies that avoids complications associated with the use of human pluripotent stem cells.

Date: 2010
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DOI: 10.1038/nature09591

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