Nature 468, 521-526 (25 November 2010) | doi:10.1038/nature09591; Received 17 August 2010;
Accepted 20 October 2010; Published online 7 November 2010
Direct conversion of human fibroblasts to multilineage blood progenitors Eva Szabo1, Shravanti Rampalli1, Ruth M. Risueño1, Angelique Schnerch1,2, Ryan Mitchell1,2,
Aline Fiebig-Comyn1, Marilyne Levadoux-Martin1 & Mickie Bhatia1,2
1.Stem Cell and Cancer Research Institute, McMaster University, Hamilton, Ontario, Canada L8N 3Z5
2.Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada L8N 3Z5
Correspondence to: Mickie Bhatia1,2 Email:
mbhatia@mcmaster.ca 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.