Sox17 Dependence Distinguishes the Transcriptional Regulation of Fetal from Adult Hematopoietic Stem Cells

Injune Kim; Thomas L. Saunders; Sean J. Morrison

doi:10.1016/j.cell.2007.06.011

Sox17 Dependence Distinguishes the Transcriptional Regulation of Fetal from Adult Hematopoietic Stem Cells

Injune Kim, Thomas L. Saunders, Sean J. Morrison

Research output: Contribution to journal › Article › peer-review

336 Scopus citations

Abstract

Fetal stem cells differ phenotypically and functionally from adult stem cells in diverse tissues. However, little is known about how these differences are regulated. To address this we compared the gene expression profiles of fetal versus adult hematopoietic stem cells (HSCs) and discovered that the Sox17 transcriptional regulator is specifically expressed in fetal and neonatal but not adult HSCs. Germline deletion of Sox17 led to severe fetal hematopoietic defects, including a lack of detectable definitive HSCs. Conditional deletion of Sox17 from hematopoietic cells led to the loss of fetal and neonatal but not adult HSCs. HSCs stopped expressing Sox17 approximately 4 weeks after birth. During this transition, loss of Sox17 expression correlated with slower proliferation and the acquisition of an adult phenotype by individual HSCs. Sox17 is thus required for the maintenance of fetal and neonatal HSCs and distinguishes their transcriptional regulation from adult HSCs.

Original language	English (US)
Pages (from-to)	470-483
Number of pages	14
Journal	Cell
Volume	130
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2007.06.011
State	Published - Aug 10 2007

Keywords

DEVBIO
STEMCELL

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.cell.2007.06.011

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title = "Sox17 Dependence Distinguishes the Transcriptional Regulation of Fetal from Adult Hematopoietic Stem Cells",

abstract = "Fetal stem cells differ phenotypically and functionally from adult stem cells in diverse tissues. However, little is known about how these differences are regulated. To address this we compared the gene expression profiles of fetal versus adult hematopoietic stem cells (HSCs) and discovered that the Sox17 transcriptional regulator is specifically expressed in fetal and neonatal but not adult HSCs. Germline deletion of Sox17 led to severe fetal hematopoietic defects, including a lack of detectable definitive HSCs. Conditional deletion of Sox17 from hematopoietic cells led to the loss of fetal and neonatal but not adult HSCs. HSCs stopped expressing Sox17 approximately 4 weeks after birth. During this transition, loss of Sox17 expression correlated with slower proliferation and the acquisition of an adult phenotype by individual HSCs. Sox17 is thus required for the maintenance of fetal and neonatal HSCs and distinguishes their transcriptional regulation from adult HSCs.",

keywords = "DEVBIO, STEMCELL",

author = "Injune Kim and Saunders, {Thomas L.} and Morrison, {Sean J.}",

note = "Funding Information: This work was supported by the Howard Hughes Medical Institute and the U.S. Army Research Laboratory/Office under grant number DAAD19-03-1-0168. Flow cytometry was partially supported by the University of Michigan Comprehensive Cancer NIH CA46592, and the University of Michigan Multipurpose Arthritis Center NIH AR20557. Antibody production was partially supported by the Rheumatic Core Disease Center (1 P30 AR48310). I.K. was supported by a postdoctoral fellowship from the University of Michigan Cancer Biology Training Program. The authors are grateful to Elizabeth Hughes for generation of gene-targeted mice, to David Adams and Martin White for flow cytometry, and to Elizabeth Smith (UM Hybridoma Core) for antibody production. ",

year = "2007",

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doi = "10.1016/j.cell.2007.06.011",

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AU - Kim, Injune

AU - Saunders, Thomas L.

AU - Morrison, Sean J.

N1 - Funding Information: This work was supported by the Howard Hughes Medical Institute and the U.S. Army Research Laboratory/Office under grant number DAAD19-03-1-0168. Flow cytometry was partially supported by the University of Michigan Comprehensive Cancer NIH CA46592, and the University of Michigan Multipurpose Arthritis Center NIH AR20557. Antibody production was partially supported by the Rheumatic Core Disease Center (1 P30 AR48310). I.K. was supported by a postdoctoral fellowship from the University of Michigan Cancer Biology Training Program. The authors are grateful to Elizabeth Hughes for generation of gene-targeted mice, to David Adams and Martin White for flow cytometry, and to Elizabeth Smith (UM Hybridoma Core) for antibody production.

PY - 2007/8/10

Y1 - 2007/8/10

N2 - Fetal stem cells differ phenotypically and functionally from adult stem cells in diverse tissues. However, little is known about how these differences are regulated. To address this we compared the gene expression profiles of fetal versus adult hematopoietic stem cells (HSCs) and discovered that the Sox17 transcriptional regulator is specifically expressed in fetal and neonatal but not adult HSCs. Germline deletion of Sox17 led to severe fetal hematopoietic defects, including a lack of detectable definitive HSCs. Conditional deletion of Sox17 from hematopoietic cells led to the loss of fetal and neonatal but not adult HSCs. HSCs stopped expressing Sox17 approximately 4 weeks after birth. During this transition, loss of Sox17 expression correlated with slower proliferation and the acquisition of an adult phenotype by individual HSCs. Sox17 is thus required for the maintenance of fetal and neonatal HSCs and distinguishes their transcriptional regulation from adult HSCs.

AB - Fetal stem cells differ phenotypically and functionally from adult stem cells in diverse tissues. However, little is known about how these differences are regulated. To address this we compared the gene expression profiles of fetal versus adult hematopoietic stem cells (HSCs) and discovered that the Sox17 transcriptional regulator is specifically expressed in fetal and neonatal but not adult HSCs. Germline deletion of Sox17 led to severe fetal hematopoietic defects, including a lack of detectable definitive HSCs. Conditional deletion of Sox17 from hematopoietic cells led to the loss of fetal and neonatal but not adult HSCs. HSCs stopped expressing Sox17 approximately 4 weeks after birth. During this transition, loss of Sox17 expression correlated with slower proliferation and the acquisition of an adult phenotype by individual HSCs. Sox17 is thus required for the maintenance of fetal and neonatal HSCs and distinguishes their transcriptional regulation from adult HSCs.

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Sox17 Dependence Distinguishes the Transcriptional Regulation of Fetal from Adult Hematopoietic Stem Cells

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Keywords

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