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Defining the Minimal Factors Required for Erythropoiesis through Direct Lineage Conversion

Capellera-Garcia, Sandra LU ; Pulecio, Julian; Dhulipala, Kishori; Siva, Kavitha LU ; Rayon-Estrada, Violeta; Singbrant, Sofie LU ; Sommarin, Mikael N E LU ; Walkley, Carl R; Soneji, Shamit LU and Karlsson, Göran LU , et al. (2016) In Cell Reports 15(11). p.2550-2562
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 or Myb to the GTLM cocktail resulted in iEPs... (More)

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.

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@article{f6b19b89-7af1-4e4a-9f10-a7b449477499,
  abstract     = {<p>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.</p>},
  author       = {Capellera-Garcia, Sandra and Pulecio, Julian and Dhulipala, Kishori and Siva, Kavitha and Rayon-Estrada, Violeta and Singbrant, Sofie and Sommarin, Mikael N E and Walkley, Carl R and Soneji, Shamit and Karlsson, Göran and Raya, Ángel and Sankaran, Vijay G and Flygare, Johan},
  issn         = {2211-1247},
  keyword      = {Erythropoiesis ,Direct Lineage Conversion,red blood cell},
  language     = {eng},
  month        = {06},
  number       = {11},
  pages        = {2550--2562},
  publisher    = {Cell Press},
  series       = {Cell Reports},
  title        = {Defining the Minimal Factors Required for Erythropoiesis through Direct Lineage Conversion},
  url          = {http://dx.doi.org/10.1016/j.celrep.2016.05.027},
  volume       = {15},
  year         = {2016},
}