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Induction of a hemogenic program in mouse fibroblasts

Pereira, Carlos Filipe LU ; Chang, Betty; Qiu, Jiajing; Niu, Xiaohong; Papatsenko, Dmitri; Hendry, Caroline E.; Clark, Neil R.; Nomura-Kitabayashi, Aya; Kovacic, Jason C. and Ma'Ayan, Avi, et al. (2013) In Cell Stem Cell 13(2). p.205-218
Abstract

Definitive hematopoiesis emerges during embryogenesis via an endothelial-to-hematopoietic transition. We attempted to induce this process in mouse fibroblasts by screening a panel of factors for hemogenic activity. We identified a combination of four transcription factors, Gata2, Gfi1b, cFos, and Etv6, that efficiently induces endothelial-like precursor cells, with the subsequent appearance of hematopoietic cells. The precursor cells express a human CD34 reporter, Sca1, and Prominin1 within a global endothelial transcription program. Emergent hematopoietic cells possess nascent hematopoietic stem cell gene-expression profiles and cell-surface phenotypes. After transgene silencing and reaggregation culture, the specified cells generate... (More)

Definitive hematopoiesis emerges during embryogenesis via an endothelial-to-hematopoietic transition. We attempted to induce this process in mouse fibroblasts by screening a panel of factors for hemogenic activity. We identified a combination of four transcription factors, Gata2, Gfi1b, cFos, and Etv6, that efficiently induces endothelial-like precursor cells, with the subsequent appearance of hematopoietic cells. The precursor cells express a human CD34 reporter, Sca1, and Prominin1 within a global endothelial transcription program. Emergent hematopoietic cells possess nascent hematopoietic stem cell gene-expression profiles and cell-surface phenotypes. After transgene silencing and reaggregation culture, the specified cells generate hematopoietic colonies in vitro. Thus, we show that a simple combination of transcription factors is sufficient to induce a complex, dynamic, and multistep developmental program in vitro. These findings provide insights into the specification of definitive hemogenesis and a platform for future development of patient-specific stem and progenitor cells, as well as more-differentiated blood products.

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published
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Cell Stem Cell
volume
13
issue
2
pages
14 pages
publisher
Cell Press
external identifiers
  • scopus:84881149632
ISSN
1934-5909
DOI
10.1016/j.stem.2013.05.024
language
English
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no
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6fc311ab-0cce-489d-8990-3282cead35d6
date added to LUP
2017-10-02 17:27:51
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2018-12-09 04:34:04
@article{6fc311ab-0cce-489d-8990-3282cead35d6,
  abstract     = {<p>Definitive hematopoiesis emerges during embryogenesis via an endothelial-to-hematopoietic transition. We attempted to induce this process in mouse fibroblasts by screening a panel of factors for hemogenic activity. We identified a combination of four transcription factors, Gata2, Gfi1b, cFos, and Etv6, that efficiently induces endothelial-like precursor cells, with the subsequent appearance of hematopoietic cells. The precursor cells express a human CD34 reporter, Sca1, and Prominin1 within a global endothelial transcription program. Emergent hematopoietic cells possess nascent hematopoietic stem cell gene-expression profiles and cell-surface phenotypes. After transgene silencing and reaggregation culture, the specified cells generate hematopoietic colonies in vitro. Thus, we show that a simple combination of transcription factors is sufficient to induce a complex, dynamic, and multistep developmental program in vitro. These findings provide insights into the specification of definitive hemogenesis and a platform for future development of patient-specific stem and progenitor cells, as well as more-differentiated blood products.</p>},
  author       = {Pereira, Carlos Filipe and Chang, Betty and Qiu, Jiajing and Niu, Xiaohong and Papatsenko, Dmitri and Hendry, Caroline E. and Clark, Neil R. and Nomura-Kitabayashi, Aya and Kovacic, Jason C. and Ma'Ayan, Avi and Schaniel, Christoph and Lemischka, Ihor R. and Moore, Kateri},
  issn         = {1934-5909},
  language     = {eng},
  month        = {08},
  number       = {2},
  pages        = {205--218},
  publisher    = {Cell Press},
  series       = {Cell Stem Cell},
  title        = {Induction of a hemogenic program in mouse fibroblasts},
  url          = {http://dx.doi.org/10.1016/j.stem.2013.05.024},
  volume       = {13},
  year         = {2013},
}