Slug deficiency enhances self-renewal of hematopoietic stem cells during hematopoietic regeneration

Yan Sun, Lijian Shao, Hao Bai, Zack Z. Wang, Wen Shu Wu

Research output: Contribution to journalArticle

Abstract

Both extrinsic and intrinsic mechanisms tightly govern hematopoietic stem cell (HSC) decisions of self-renewal and differentiation. However, transcription factors that can selectively regulate HSC self-renewal division after stress remain to be identified. Slug is an evolutionarily conserved zinc-finger transcription factor that is highly expressed in primitive hematopoietic cells and is critical for the radioprotection of these key cells. We studied the effect of Slug in the regulation of HSCs in Slug-deficient mice under normal and stress conditions using serial functional assays. Here, we show that Slug deficiency does not disturb hematopoiesis or alter HSC homeostasis and differentiation in bone marrow but increases the numbers of primitive hematopoietic cells in the extramedullary spleen site. Deletion of Slug enhances HSC repopulating potential but not its homing and differentiation ability. Furthermore, Slug deficiency increases HSC proliferation and repopulating potential in vivo after myelo-suppression and accelerates HSC expansion during in vitro culture. Therefore, we propose that Slug is essential for controlling the transition of HSCs from relative quiescence under steady-state condition to rapid proliferation under stress conditions. Our data suggest that inhibition of Slug in HSCs may present a novel strategy for accelerating hematopoietic recovery, thus providing therapeutic benefits for patients after clinical myelo-suppressive treatment.

Original languageEnglish (US)
Pages (from-to)1709-1717
Number of pages9
JournalBlood
Volume115
Issue number9
DOIs
StatePublished - Mar 4 2010
Externally publishedYes

Fingerprint

Gastropoda
Hematopoietic Stem Cells
Stem cells
Regeneration
Transcription Factors
Cell proliferation
Cell culture
Zinc
Assays
Zinc Fingers
Hematopoiesis
Bone
Cell Differentiation
Recovery
Homeostasis
Spleen
Bone Marrow
Cell Proliferation
Therapeutics

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Slug deficiency enhances self-renewal of hematopoietic stem cells during hematopoietic regeneration. / Sun, Yan; Shao, Lijian; Bai, Hao; Wang, Zack Z.; Wu, Wen Shu.

In: Blood, Vol. 115, No. 9, 04.03.2010, p. 1709-1717.

Research output: Contribution to journalArticle

Sun, Yan ; Shao, Lijian ; Bai, Hao ; Wang, Zack Z. ; Wu, Wen Shu. / Slug deficiency enhances self-renewal of hematopoietic stem cells during hematopoietic regeneration. In: Blood. 2010 ; Vol. 115, No. 9. pp. 1709-1717.
@article{d76e7da9bbbb48fca7e25d5dab79919f,
title = "Slug deficiency enhances self-renewal of hematopoietic stem cells during hematopoietic regeneration",
abstract = "Both extrinsic and intrinsic mechanisms tightly govern hematopoietic stem cell (HSC) decisions of self-renewal and differentiation. However, transcription factors that can selectively regulate HSC self-renewal division after stress remain to be identified. Slug is an evolutionarily conserved zinc-finger transcription factor that is highly expressed in primitive hematopoietic cells and is critical for the radioprotection of these key cells. We studied the effect of Slug in the regulation of HSCs in Slug-deficient mice under normal and stress conditions using serial functional assays. Here, we show that Slug deficiency does not disturb hematopoiesis or alter HSC homeostasis and differentiation in bone marrow but increases the numbers of primitive hematopoietic cells in the extramedullary spleen site. Deletion of Slug enhances HSC repopulating potential but not its homing and differentiation ability. Furthermore, Slug deficiency increases HSC proliferation and repopulating potential in vivo after myelo-suppression and accelerates HSC expansion during in vitro culture. Therefore, we propose that Slug is essential for controlling the transition of HSCs from relative quiescence under steady-state condition to rapid proliferation under stress conditions. Our data suggest that inhibition of Slug in HSCs may present a novel strategy for accelerating hematopoietic recovery, thus providing therapeutic benefits for patients after clinical myelo-suppressive treatment.",
author = "Yan Sun and Lijian Shao and Hao Bai and Wang, {Zack Z.} and Wu, {Wen Shu}",
year = "2010",
month = "3",
day = "4",
doi = "10.1182/blood-2009-07-232934",
language = "English (US)",
volume = "115",
pages = "1709--1717",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "9",

}

TY - JOUR

T1 - Slug deficiency enhances self-renewal of hematopoietic stem cells during hematopoietic regeneration

AU - Sun, Yan

AU - Shao, Lijian

AU - Bai, Hao

AU - Wang, Zack Z.

AU - Wu, Wen Shu

PY - 2010/3/4

Y1 - 2010/3/4

N2 - Both extrinsic and intrinsic mechanisms tightly govern hematopoietic stem cell (HSC) decisions of self-renewal and differentiation. However, transcription factors that can selectively regulate HSC self-renewal division after stress remain to be identified. Slug is an evolutionarily conserved zinc-finger transcription factor that is highly expressed in primitive hematopoietic cells and is critical for the radioprotection of these key cells. We studied the effect of Slug in the regulation of HSCs in Slug-deficient mice under normal and stress conditions using serial functional assays. Here, we show that Slug deficiency does not disturb hematopoiesis or alter HSC homeostasis and differentiation in bone marrow but increases the numbers of primitive hematopoietic cells in the extramedullary spleen site. Deletion of Slug enhances HSC repopulating potential but not its homing and differentiation ability. Furthermore, Slug deficiency increases HSC proliferation and repopulating potential in vivo after myelo-suppression and accelerates HSC expansion during in vitro culture. Therefore, we propose that Slug is essential for controlling the transition of HSCs from relative quiescence under steady-state condition to rapid proliferation under stress conditions. Our data suggest that inhibition of Slug in HSCs may present a novel strategy for accelerating hematopoietic recovery, thus providing therapeutic benefits for patients after clinical myelo-suppressive treatment.

AB - Both extrinsic and intrinsic mechanisms tightly govern hematopoietic stem cell (HSC) decisions of self-renewal and differentiation. However, transcription factors that can selectively regulate HSC self-renewal division after stress remain to be identified. Slug is an evolutionarily conserved zinc-finger transcription factor that is highly expressed in primitive hematopoietic cells and is critical for the radioprotection of these key cells. We studied the effect of Slug in the regulation of HSCs in Slug-deficient mice under normal and stress conditions using serial functional assays. Here, we show that Slug deficiency does not disturb hematopoiesis or alter HSC homeostasis and differentiation in bone marrow but increases the numbers of primitive hematopoietic cells in the extramedullary spleen site. Deletion of Slug enhances HSC repopulating potential but not its homing and differentiation ability. Furthermore, Slug deficiency increases HSC proliferation and repopulating potential in vivo after myelo-suppression and accelerates HSC expansion during in vitro culture. Therefore, we propose that Slug is essential for controlling the transition of HSCs from relative quiescence under steady-state condition to rapid proliferation under stress conditions. Our data suggest that inhibition of Slug in HSCs may present a novel strategy for accelerating hematopoietic recovery, thus providing therapeutic benefits for patients after clinical myelo-suppressive treatment.

UR - http://www.scopus.com/inward/record.url?scp=77950353236&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950353236&partnerID=8YFLogxK

U2 - 10.1182/blood-2009-07-232934

DO - 10.1182/blood-2009-07-232934

M3 - Article

C2 - 20032500

AN - SCOPUS:77950353236

VL - 115

SP - 1709

EP - 1717

JO - Blood

JF - Blood

SN - 0006-4971

IS - 9

ER -