Tel1/ETV6 specifies blood stem cells through the agency of VEGF signaling.
The regulation of stem cell ontogeny is poorly understood. We show that the leukemia-associated Ets transcription factor, Tel1/ETV6, specifies the first hematopoietic stem cells (HSCs) in the dorsal aorta (DA). In contrast, Tel1/ETV6 has little effect on embryonic blood formation, further distinguis...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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2010
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| _version_ | 1826263619326705664 |
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| author | Ciau-Uitz, A Pinheiro, P Gupta, R Enver, T Patient, R |
| author_facet | Ciau-Uitz, A Pinheiro, P Gupta, R Enver, T Patient, R |
| author_sort | Ciau-Uitz, A |
| collection | OXFORD |
| description | The regulation of stem cell ontogeny is poorly understood. We show that the leukemia-associated Ets transcription factor, Tel1/ETV6, specifies the first hematopoietic stem cells (HSCs) in the dorsal aorta (DA). In contrast, Tel1/ETV6 has little effect on embryonic blood formation, further distinguishing the programming of the long- and short-term blood populations. Consistent with the notion of concordance of arterial and HSC programs, we show that Tel1/ETV6 is also required for the specification of the DA as an artery. We further show that Tel1/ETV6 acts by regulating the transcription of VegfA in both the lateral plate mesoderm and also in the somites. Exogenous VEGFA rescues Tel1/ETV6 morphants, and depletion of VEGFA or its receptor, Flk1, largely phenocopies Tel1/ETV6 depletion. Few such links between intrinsic and extrinsic programming of stem cells have been reported previously. Our data place Tel1/ETV6 at the apex of the genetic regulatory cascade leading to HSC production. |
| first_indexed | 2024-03-06T19:54:40Z |
| format | Journal article |
| id | oxford-uuid:25252cf5-f551-44d6-a735-bd9c4cb15bb1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:54:40Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:25252cf5-f551-44d6-a735-bd9c4cb15bb12022-03-26T11:54:09ZTel1/ETV6 specifies blood stem cells through the agency of VEGF signaling.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:25252cf5-f551-44d6-a735-bd9c4cb15bb1EnglishSymplectic Elements at Oxford2010Ciau-Uitz, APinheiro, PGupta, REnver, TPatient, RThe regulation of stem cell ontogeny is poorly understood. We show that the leukemia-associated Ets transcription factor, Tel1/ETV6, specifies the first hematopoietic stem cells (HSCs) in the dorsal aorta (DA). In contrast, Tel1/ETV6 has little effect on embryonic blood formation, further distinguishing the programming of the long- and short-term blood populations. Consistent with the notion of concordance of arterial and HSC programs, we show that Tel1/ETV6 is also required for the specification of the DA as an artery. We further show that Tel1/ETV6 acts by regulating the transcription of VegfA in both the lateral plate mesoderm and also in the somites. Exogenous VEGFA rescues Tel1/ETV6 morphants, and depletion of VEGFA or its receptor, Flk1, largely phenocopies Tel1/ETV6 depletion. Few such links between intrinsic and extrinsic programming of stem cells have been reported previously. Our data place Tel1/ETV6 at the apex of the genetic regulatory cascade leading to HSC production. |
| spellingShingle | Ciau-Uitz, A Pinheiro, P Gupta, R Enver, T Patient, R Tel1/ETV6 specifies blood stem cells through the agency of VEGF signaling. |
| title | Tel1/ETV6 specifies blood stem cells through the agency of VEGF signaling. |
| title_full | Tel1/ETV6 specifies blood stem cells through the agency of VEGF signaling. |
| title_fullStr | Tel1/ETV6 specifies blood stem cells through the agency of VEGF signaling. |
| title_full_unstemmed | Tel1/ETV6 specifies blood stem cells through the agency of VEGF signaling. |
| title_short | Tel1/ETV6 specifies blood stem cells through the agency of VEGF signaling. |
| title_sort | tel1 etv6 specifies blood stem cells through the agency of vegf signaling |
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