Publication Date:
2010-11-09
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Szabo, Eva -- Rampalli, Shravanti -- Risueno, Ruth M -- Schnerch, Angelique -- Mitchell, Ryan -- Fiebig-Comyn, Aline -- Levadoux-Martin, Marilyne -- Bhatia, Mickie -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2010 Nov 25;468(7323):521-6. doi: 10.1038/nature09591. Epub 2010 Nov 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stem Cell and Cancer Research Institute, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21057492" target="_blank"〉PubMed〈/a〉
Keywords:
Cell Culture Techniques/*methods
;
*Cell Differentiation
;
Dermis/cytology
;
Fibroblasts/*cytology
;
Hematopoietic Stem Cells/*cytology
;
Humans
;
Pluripotent Stem Cells/cytology/metabolism
;
Stem Cells/*cytology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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