Defining the Minimal Factors Required for Erythropoiesis through Direct Lineage Conversion
(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.
(Less)
- author
- organization
-
- Stem cell and red cell biology (research group)
- Division of Molecular Medicine and Gene Therapy
- Division of Molecular Hematology (DMH)
- Conputational Genomics Group (research group)
- Stem Cells and Leukemia (research group)
- Stem Cells to Red Blood Cells (research group)
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
- publishing date
- 2016-06-14
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Erythropoiesis, Direct Lineage Conversion, red blood cell
- in
- Cell Reports
- volume
- 15
- issue
- 11
- pages
- 13 pages
- publisher
- Cell Press
- external identifiers
-
- scopus:84974678251
- wos:000377776400022
- pmid:27264182
- ISSN
- 2211-1247
- DOI
- 10.1016/j.celrep.2016.05.027
- language
- English
- LU publication?
- yes
- id
- f6b19b89-7af1-4e4a-9f10-a7b449477499
- date added to LUP
- 2016-09-22 13:27:08
- date last changed
- 2024-09-06 22:24:11
@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}}, keywords = {{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}}, doi = {{10.1016/j.celrep.2016.05.027}}, volume = {{15}}, year = {{2016}}, }