Journal article
Defining the Minimal Factors Required for Erythropoiesis through Direct Lineage Conversion
S Capellera-Garcia, J Pulecio, K Dhulipala, K Siva, V Rayon-Estrada, S Singbrant, MNE Sommarin, CR Walkley, S Soneji, G Karlsson, Á Raya, VG Sankaran, J Flygare
Cell Reports | CELL PRESS | Published : 2016
Abstract
Erythroid cell commitment and differentiation proceed through activation of a lineage-restricted transcriptional network orchestrated by a group of well characterized genes. However, the minimal set of factors necessary for instructing red blood cell (RBC) development remains undefined. We employed a screen for transcription factors allowing direct lineage reprograming from fibroblasts to induced erythroid progenitors/precursors (iEPs). We show that Gata1, Tal1, Lmo2, and c-Myc (GTLM) can rapidly convert murine and human fibroblasts directly to iEPs. The transcriptional signature of murine iEPs resembled mainly that of primitive erythroid progenitors in the yolk sac, whereas addition of Klf1..
View full abstractGrants
Awarded by Fundació la Marató de TV3
Funding Acknowledgements
We thank Evelyn Wang and Gregory Hyde (Whitehead Institute, Cambridge, MA) for cloning and Harvey Lodish (Whitehead Institute) for providing many of the plasmids used for generating the retroviral library. We thank Jacob Ulirsch (Broad Institute of MIT and Harvard) for early contributions to the global gene expression analysis. We thank Roger Ronn (Department of Molecular Medicine and Gene Therapy) for input on the manuscript and Zhi Ma (Lund Stem Cell Center) for flow cytometry assistance. This work was supported by the Ragnar Soderberg Foundation (to J.F.); the Swedish Research Council (to J.F.); Stiftelsen Olle Engkvist Byggmastare (to J.F.); the Swedish Foundation for Strategic Research (to J.F.); Ake Wiberg's Foundation (to J.F.); a Marie Curie integration grant (to J.F.); and grants from MINECO (SAF2012-33526) (to A.R.), ISCIII - FEDER (RETICS RD12/0019/0019, RD12/0019/0034) (to A.R.), Fundacio Marato de TV3 (121430) (to A.R.), and AGAUR (2014-SGR-1460, 2014-SGR-1570) (to A.R.). J.P. was partially supported by a Juan de la Cierva postdoctoral fellowship (JCI-2012-15293).