Defining the Minimal Factors Required for Erythropoiesis through Direct Lineage Conversion
Name
Defining the Minimal Factors.pdf
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4.35 MB
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Checksum (MD5)
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Author(s)
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
Date Issued
June 2016
Journal
Cell Reports
Publisher
Elsevier
Citation
Capellera-Garcia, Sandra; Pulecio, Julian; Dhulipala, Kishori; Siva, Kavitha; Rayon-Estrada, Violeta et al. "Defining the Minimal Factors Required for Erythropoiesis through Direct Lineage Conversion." Cell Reports 15, 11 (June 2016): 2550–2562 © 2016 The Author(s)
Version
Final published version
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 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.
MIT Department
Broad Institute of MIT and Harvard
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2016.05.027
