The differential activities of Runx1 promoters define milestones during embryonic hematopoiesis.

2.50
Hdl Handle:
http://hdl.handle.net/10541/91615
Title:
The differential activities of Runx1 promoters define milestones during embryonic hematopoiesis.
Authors:
Sroczynska, Patrycja; Lancrin, Christophe; Kouskoff, Valerie; Lacaud, Georges
Abstract:
The transcription factor RUNX1/AML1 is a master regulator of hematopoietic development. Its spatiotemporal expression is tightly regulated during embryonic development and is under the control of 2 alternative promoters, distal and proximal. Despite the functional significance of Runx1, the relative and specific activities of these 2 promoters remain largely uncharacterized. To investigate these activities, we introduced 2 reporter genes under the control of the proximal and distal promoters in embryonic stem cell and transgenic mouse lines. Our study reveals that both in vitro and in vivo the proximal Runx1 isoform marks a hemogenic endothelium cell population, whereas the subsequent expression of distal Runx1 defines fully committed definitive hematopoietic progenitors. Interestingly, hematopoietic commitment in distal Runx1 knockout embryos appears normal. Altogether, our data demonstrate that the differential activities of the 2 Runx1 promoters define milestones of hematopoietic development and suggest that the proximal isoform plays a critical role in the generation of hematopoietic cells from hemogenic endothelium. Identification and access to the discrete stages of hematopoietic development defined by the activities of the Runx1 promoters will provide the opportunity to further explore the cellular and molecular mechanisms of hematopoietic development.
Affiliation:
Cancer Research UK Stem Cell Biology Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, United Kingdom.
Citation:
The differential activities of Runx1 promoters define milestones during embryonic hematopoiesis. 2009, 114 (26):5279-89 Blood
Journal:
Blood
Issue Date:
17-Dec-2009
URI:
http://hdl.handle.net/10541/91615
DOI:
10.1182/blood-2009-05-222307
PubMed ID:
19858498
Language:
en
ISSN:
1528-0020
Appears in Collections:
All Paterson Institute for Cancer Research; Stem Cell and Haematopoiesis; Stem Cell Biology

Full metadata record

DC FieldValue Language
dc.contributor.authorSroczynska, Patrycjaen
dc.contributor.authorLancrin, Christopheen
dc.contributor.authorKouskoff, Valerieen
dc.contributor.authorLacaud, Georgesen
dc.date.accessioned2010-02-09T14:37:11Z-
dc.date.available2010-02-09T14:37:11Z-
dc.date.issued2009-12-17-
dc.identifier.citationThe differential activities of Runx1 promoters define milestones during embryonic hematopoiesis. 2009, 114 (26):5279-89 Blooden
dc.identifier.issn1528-0020-
dc.identifier.pmid19858498-
dc.identifier.doi10.1182/blood-2009-05-222307-
dc.identifier.urihttp://hdl.handle.net/10541/91615-
dc.description.abstractThe transcription factor RUNX1/AML1 is a master regulator of hematopoietic development. Its spatiotemporal expression is tightly regulated during embryonic development and is under the control of 2 alternative promoters, distal and proximal. Despite the functional significance of Runx1, the relative and specific activities of these 2 promoters remain largely uncharacterized. To investigate these activities, we introduced 2 reporter genes under the control of the proximal and distal promoters in embryonic stem cell and transgenic mouse lines. Our study reveals that both in vitro and in vivo the proximal Runx1 isoform marks a hemogenic endothelium cell population, whereas the subsequent expression of distal Runx1 defines fully committed definitive hematopoietic progenitors. Interestingly, hematopoietic commitment in distal Runx1 knockout embryos appears normal. Altogether, our data demonstrate that the differential activities of the 2 Runx1 promoters define milestones of hematopoietic development and suggest that the proximal isoform plays a critical role in the generation of hematopoietic cells from hemogenic endothelium. Identification and access to the discrete stages of hematopoietic development defined by the activities of the Runx1 promoters will provide the opportunity to further explore the cellular and molecular mechanisms of hematopoietic development.en
dc.language.isoenen
dc.subjectHematopoiesisen
dc.subjectHaematopoietic Stem Cellsen
dc.subject.meshAnimals-
dc.subject.meshCell Differentiation-
dc.subject.meshCoculture Techniques-
dc.subject.meshCore Binding Factor Alpha 2 Subunit-
dc.subject.meshEmbryo, Mammalian-
dc.subject.meshEmbryonic Development-
dc.subject.meshEmbryonic Stem Cells-
dc.subject.meshEndothelium, Vascular-
dc.subject.meshFlow Cytometry-
dc.subject.meshGene Expression-
dc.subject.meshGene Expression Regulation, Developmental-
dc.subject.meshHematopoiesis-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshMice-
dc.subject.meshMice, Knockout-
dc.subject.meshPolymerase Chain Reaction-
dc.subject.meshPromoter Regions, Genetic-
dc.subject.meshProtein Isoforms-
dc.titleThe differential activities of Runx1 promoters define milestones during embryonic hematopoiesis.en
dc.contributor.departmentCancer Research UK Stem Cell Biology Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, United Kingdom.en
dc.identifier.journalBlooden

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