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CCAAT/enhancer binding protein alpha (C/EBP alpha)-induced transdifferentiation of pre-B cells into macrophages involves no overt retrodifferentiation

Di Tullio, Alessandro; Phong Vu Manh, Thien; Schubert, Alexis; Månsson, Robert LU and Graf, Thomas (2011) In Proceedings of the National Academy of Sciences 108(41). p.17016-17021
Abstract
Earlier work has shown that pre-B cells can be converted into macrophages by the transcription factor CCAAT/enhancer binding protein a at very high frequencies. Using this system, we performed a systematic analysis of whether during transdifferentiation the cells transiently reactivate progenitor-restricted genes or even retrodifferentiate. A transcriptome analysis of transdifferentiating cells showed that most genes are up-or down-regulated continuously, acquiring a macrophage phenotype within 5 d. In addition, we observed the transient reactivation of a subset of immature myeloid markers, as well as low levels of the progenitor markers Kit and FMS-like tyrosine kinase 3 and a few lineage-inappropriate genes. Importantly, however, we were... (More)
Earlier work has shown that pre-B cells can be converted into macrophages by the transcription factor CCAAT/enhancer binding protein a at very high frequencies. Using this system, we performed a systematic analysis of whether during transdifferentiation the cells transiently reactivate progenitor-restricted genes or even retrodifferentiate. A transcriptome analysis of transdifferentiating cells showed that most genes are up-or down-regulated continuously, acquiring a macrophage phenotype within 5 d. In addition, we observed the transient reactivation of a subset of immature myeloid markers, as well as low levels of the progenitor markers Kit and FMS-like tyrosine kinase 3 and a few lineage-inappropriate genes. Importantly, however, we were unable to observe the reexpression of cell-surface marker combinations that characterize hematopoietic stem and progenitor cells, including c-Kit and FMS-like tyrosine kinase 3, even when CAAT/enhancer binding protein a was activated in pre-B cells under culture conditions that favor growth of hematopoietic stem and progenitor cells or when the transcription factor was activated in a time-limited fashion. Together, our findings are consistent with the notion that the conversion from pre-B cells to macrophages is mostly direct and does not involve overt retrodifferentiation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cell fate decision, cell reprogramming, hematopoietic differentiation, lineage commitment
in
Proceedings of the National Academy of Sciences
volume
108
issue
41
pages
17016 - 17021
publisher
National Acad Sciences
external identifiers
  • wos:000295973800033
  • scopus:80054746874
ISSN
1091-6490
DOI
10.1073/pnas.1112169108
language
English
LU publication?
yes
id
501dcad6-28f9-45b7-9338-ea0263adb473 (old id 2211646)
date added to LUP
2011-12-01 08:29:42
date last changed
2017-11-12 03:09:00
@article{501dcad6-28f9-45b7-9338-ea0263adb473,
  abstract     = {Earlier work has shown that pre-B cells can be converted into macrophages by the transcription factor CCAAT/enhancer binding protein a at very high frequencies. Using this system, we performed a systematic analysis of whether during transdifferentiation the cells transiently reactivate progenitor-restricted genes or even retrodifferentiate. A transcriptome analysis of transdifferentiating cells showed that most genes are up-or down-regulated continuously, acquiring a macrophage phenotype within 5 d. In addition, we observed the transient reactivation of a subset of immature myeloid markers, as well as low levels of the progenitor markers Kit and FMS-like tyrosine kinase 3 and a few lineage-inappropriate genes. Importantly, however, we were unable to observe the reexpression of cell-surface marker combinations that characterize hematopoietic stem and progenitor cells, including c-Kit and FMS-like tyrosine kinase 3, even when CAAT/enhancer binding protein a was activated in pre-B cells under culture conditions that favor growth of hematopoietic stem and progenitor cells or when the transcription factor was activated in a time-limited fashion. Together, our findings are consistent with the notion that the conversion from pre-B cells to macrophages is mostly direct and does not involve overt retrodifferentiation.},
  author       = {Di Tullio, Alessandro and Phong Vu Manh, Thien and Schubert, Alexis and Månsson, Robert and Graf, Thomas},
  issn         = {1091-6490},
  keyword      = {cell fate decision,cell reprogramming,hematopoietic differentiation,lineage commitment},
  language     = {eng},
  number       = {41},
  pages        = {17016--17021},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {CCAAT/enhancer binding protein alpha (C/EBP alpha)-induced transdifferentiation of pre-B cells into macrophages involves no overt retrodifferentiation},
  url          = {http://dx.doi.org/10.1073/pnas.1112169108},
  volume       = {108},
  year         = {2011},
}