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Induction of a hemogenic program in mouse fibroblasts

Pereira, Carlos Filipe LU orcid ; 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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publishing date
type
Contribution to journal
publication status
published
in
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
LU publication?
no
id
6fc311ab-0cce-489d-8990-3282cead35d6
date added to LUP
2017-10-02 17:27:51
date last changed
2022-04-01 19:45:36
@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}},
  doi          = {{10.1016/j.stem.2013.05.024}},
  volume       = {{13}},
  year         = {{2013}},
}