CCAAT/enhancer binding protein alpha (C/EBP alpha)-induced transdifferentiation of pre-B cells into macrophages involves no overt retrodifferentiation
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2211646
- author
- Di Tullio, Alessandro ; Phong Vu Manh, Thien ; Schubert, Alexis ; Månsson, Robert LU and Graf, Thomas
- organization
- publishing date
- 2011
- 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 Academy of Sciences
- external identifiers
-
- wos:000295973800033
- scopus:80054746874
- pmid:21969581
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.1112169108
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Hematopoietic Stem Cell Laboratory (013022012)
- id
- 501dcad6-28f9-45b7-9338-ea0263adb473 (old id 2211646)
- date added to LUP
- 2016-04-01 10:32:17
- date last changed
- 2022-08-05 07:50:14
@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}},
keywords = {{cell fate decision; cell reprogramming; hematopoietic differentiation; lineage commitment}},
language = {{eng}},
number = {{41}},
pages = {{17016--17021}},
publisher = {{National Academy of 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}},
doi = {{10.1073/pnas.1112169108}},
volume = {{108}},
year = {{2011}},
}