Induction of a hemogenic program in mouse fibroblasts
(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.
(Less)
- author
- publishing date
- 2013-08-01
- 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}}, }