Sox17 expression confers self-renewal potential and fetal stem cell characteristics upon adult hematopoietic progenitors

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A key question concerns the mechanisms that determine temporal identity in stem cells. Fetal hematopoietic stem cells (HSCs) differ from adult HSCs in terms of gene expression profile, surface marker expression, differentiation, and self-renewal capacity. We previously showed that the transcription factor SOX17 is expressed by fetal, but not adult, HSCs and is required for the maintenance of fetal and neonatal, but not adult, HSCs. In the current study, we show that ectopic expression of Sox17 in adult HSCs and transiently reconstituting multipotent progenitors was sufficient to confer increased self-renewal potential and the expression of fetal HSC genes, including fetal HSC surface markers. Sox17 expression enabled transiently reconstituting adult progenitors to give long-term multilineage reconstitution that resembled fetal hematopoiesis, including increased erythropoiesis, increased myelopoiesis, and decreased lymphopoiesis. Long-term ectopic expression of Sox17 eventually led to leukemogenesis. These data demonstrate that SOX17 is sufficient to confer fetal HSC characteristics to adult hematopoietic progenitors and is therefore a key determinant of fetal HSC identity.
Publisher
COLD SPRING HARBOR LAB PRESS
Issue Date
2011-08
Language
English
Article Type
Article
Keywords

RECEPTOR TYROSINE KINASES; SLAM FAMILY RECEPTORS; LONG-TERM; YOLK-SAC; DEPENDENCE DISTINGUISHES; BONE-MARROW; MICE; LIVER; MOUSE; DIFFERENTIATION

Citation

GENES DEVELOPMENT, v.25, no.15, pp.1613 - 1627

ISSN
0890-9369
URI
http://hdl.handle.net/10203/101452
Appears in Collection
MSE-Journal Papers(저널논문)
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