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Defining the Minimal Factors Required for Erythropoiesis through Direct Lineage Conversion

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...

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Autores principales: Capellera-Garcia, Sandra, Pulecio, Julian, Dhulipala, Kishori, Siva, Kavitha, Rayon-Estrada, Violeta, Singbrant, Sofie, Sommarin, Mikael N.E., Walkley, Carl R., Soneji, Shamit, Karlsson, Göran, Raya, Ángel, Sankaran, Vijay G., Flygare, Johan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914771/
https://www.ncbi.nlm.nih.gov/pubmed/27264182
http://dx.doi.org/10.1016/j.celrep.2016.05.027
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author Capellera-Garcia, Sandra
Pulecio, Julian
Dhulipala, Kishori
Siva, Kavitha
Rayon-Estrada, Violeta
Singbrant, Sofie
Sommarin, Mikael N.E.
Walkley, Carl R.
Soneji, Shamit
Karlsson, Göran
Raya, Ángel
Sankaran, Vijay G.
Flygare, Johan
author_facet Capellera-Garcia, Sandra
Pulecio, Julian
Dhulipala, Kishori
Siva, Kavitha
Rayon-Estrada, Violeta
Singbrant, Sofie
Sommarin, Mikael N.E.
Walkley, Carl R.
Soneji, Shamit
Karlsson, Göran
Raya, Ángel
Sankaran, Vijay G.
Flygare, Johan
author_sort Capellera-Garcia, Sandra
collection PubMed
description 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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spelling pubmed-49147712016-06-29 Defining the Minimal Factors Required for Erythropoiesis through Direct Lineage Conversion Capellera-Garcia, Sandra Pulecio, Julian Dhulipala, Kishori Siva, Kavitha Rayon-Estrada, Violeta Singbrant, Sofie Sommarin, Mikael N.E. Walkley, Carl R. Soneji, Shamit Karlsson, Göran Raya, Ángel Sankaran, Vijay G. Flygare, Johan Cell Rep Article 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. Cell Press 2016-06-02 /pmc/articles/PMC4914771/ /pubmed/27264182 http://dx.doi.org/10.1016/j.celrep.2016.05.027 Text en © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Capellera-Garcia, Sandra
Pulecio, Julian
Dhulipala, Kishori
Siva, Kavitha
Rayon-Estrada, Violeta
Singbrant, Sofie
Sommarin, Mikael N.E.
Walkley, Carl R.
Soneji, Shamit
Karlsson, Göran
Raya, Ángel
Sankaran, Vijay G.
Flygare, Johan
Defining the Minimal Factors Required for Erythropoiesis through Direct Lineage Conversion
title Defining the Minimal Factors Required for Erythropoiesis through Direct Lineage Conversion
title_full Defining the Minimal Factors Required for Erythropoiesis through Direct Lineage Conversion
title_fullStr Defining the Minimal Factors Required for Erythropoiesis through Direct Lineage Conversion
title_full_unstemmed Defining the Minimal Factors Required for Erythropoiesis through Direct Lineage Conversion
title_short Defining the Minimal Factors Required for Erythropoiesis through Direct Lineage Conversion
title_sort defining the minimal factors required for erythropoiesis through direct lineage conversion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914771/
https://www.ncbi.nlm.nih.gov/pubmed/27264182
http://dx.doi.org/10.1016/j.celrep.2016.05.027
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