TY - JOUR
T1 - Defining the Minimal Factors Required for Erythropoiesis through Direct Lineage Conversion
AU - Capellera-Garcia, Sandra
AU - Pulecio, Julian
AU - Dhulipala, Kishori
AU - Siva, Kavitha
AU - Rayon-Estrada, Violeta
AU - Singbrant, Sofie
AU - Sommarin, Mikael N.E.
AU - Walkley, Carl R.
AU - Soneji, Shamit
AU - Karlsson, Göran
AU - Raya, Ángel
AU - Sankaran, Vijay G.
AU - Flygare, Johan
N1 - Funding Information:
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 Rönn (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 Söderberg Foundation (to J.F.); the Swedish Research Council (to J.F.); Stiftelsen Olle Engkvist Byggmästare (to J.F.); the Swedish Foundation for Strategic Research (to J.F.); Åke 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.), Fundació Marató 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).
Publisher Copyright:
© 2016 The Author(s).
PY - 2016/6/14
Y1 - 2016/6/14
N2 - 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 or Myb to the GTLM cocktail resulted in iEPs with a more adult-type globin expression pattern. Our results demonstrate that direct lineage conversion is a suitable platform for defining and studying the core factors inducing the different waves of erythroid development.
AB - 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 or Myb to the GTLM cocktail resulted in iEPs with a more adult-type globin expression pattern. Our results demonstrate that direct lineage conversion is a suitable platform for defining and studying the core factors inducing the different waves of erythroid development.
UR - https://www.scopus.com/pages/publications/84974678251
U2 - 10.1016/j.celrep.2016.05.027
DO - 10.1016/j.celrep.2016.05.027
M3 - Article
C2 - 27264182
AN - SCOPUS:84974678251
SN - 2211-1247
VL - 15
SP - 2550
EP - 2562
JO - Cell Reports
JF - Cell Reports
IS - 11
ER -