Sox7-sustained expression alters the balance between proliferation and differentiation of hematopoietic progenitors at the onset of blood specification.
The molecular mechanisms that regulate the balance between proliferation and differentiation of precursors at the onset of hematopoiesis specification are poorly understood. By using a global gene expression profiling approach during the course of embryonic stem cell differentiation, we identified Sox7 as a potential candidate gene involved in the regulation of blood lineage formation from the mesoderm germ layer. In the present study, we show that Sox7 is transiently expressed in mesodermal precursors as they undergo specification to the hematopoietic program. Sox7 knockdown in vitro significantly decreases the formation of both primitive erythroid and definitive hematopoietic progenitors as well as endothelial progenitors. In contrast, Sox7-sustained expression in the earliest committed hematopoietic precursors promotes the maintenance of their multipotent and self-renewing status. Removal of this differentiation block driven by Sox7-enforced expression leads to the efficient differentiation of hematopoietic progenitors to all erythroid and myeloid lineages. This study identifies Sox7 as a novel and important player in the molecular regulation of the first committed blood precursors. Furthermore, our data demonstrate that the mere sustained expression of Sox7 is sufficient to completely alter the balance between proliferation and differentiation at the onset of hematopoiesis.
Cancer Research UK, Stem Cell Haematopoiesis Group, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester, United Kingdom.
Arnaud
A
Gandillet
Alicia G
AG
Serrano
Stella
S
Pearson
Michael
M
Lie-A-Ling
Georges
G
Lacaud
Valerie
V
Kouskoff
D000818:Animals; D002455:Cell Division; D019070:Cell Lineage; D002478:Cells, Cultured / Q000166:cytology / Q000378:metabolism; D041905:Erythroid Cells / Q000166:cytology; D005775:Gastrula / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors / Q000494:pharmacology; D055018:Hemangioblasts / Q000166:cytology / Q000378:metabolism; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000166:cytology; D034741:RNA, Small Interfering / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000502:physiology; D055760:SOXF Transcription Factors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D055760:SOXF Transcription Factors; C102515:Sox7 protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2