Fancd2-/- mice have hematopoietic defects that can be partially corrected by resveratrol

Qing-Shuo Zhang, Laura Marquez-Loza, Laura Eaton, Andrew W. Duncan, Devorah Goldman, Praveen Anur, Kevin Watanabe-Smith, R. Keaney Rathbun, William Fleming, Grover C. Bagby, Markus Grompe

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Progressive bone marrow failure is a major cause of morbidity and mortality in human Fanconi Anemia patients. In an effort to develop a Fanconi Anemia murine model to study bone marrow failure, we found that Fancd2-/- mice have readily measurable hematopoietic defects. Fancd2 deficiency was associated with a significant decline in the size of the c-Kit +Sca-1+Lineage- (KSL) pool and reduced stem cell repopulation and spleen colony-forming capacity. Fancd2-/- KSL cells showed an abnormal cell cycle status and loss of quiescence. In addition, the supportive function of the marrow microenvironment was compromised in Fancd2-/- mice. Treatment with Sirt1-mimetic and the antioxidant drug, resveratrol, maintained Fancd2-/- KSL cells in quiescence, improved the marrow micro-environment, partially corrected the abnormal cell cycle status, and significantly improved the spleen colony-forming capacity of Fancd2-/- bone marrow cells. We conclude that Fancd2-/- mice have readily quantifiable hematopoietic defects, and that this model is well suited for pharmacologic screening studies.

Original languageEnglish (US)
Pages (from-to)5140-5148
Number of pages9
JournalBlood
Volume116
Issue number24
DOIs
StatePublished - Dec 9 2010

Fingerprint

Bone
Bone Marrow
Cells
Fanconi Anemia
Defects
Cell Cycle
Spleen
Stem cells
Screening
Antioxidants
Bone Marrow Cells
Stem Cells
Morbidity
Pharmaceutical Preparations
Mortality
resveratrol
Therapeutics

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Fancd2-/- mice have hematopoietic defects that can be partially corrected by resveratrol. / Zhang, Qing-Shuo; Marquez-Loza, Laura; Eaton, Laura; Duncan, Andrew W.; Goldman, Devorah; Anur, Praveen; Watanabe-Smith, Kevin; Rathbun, R. Keaney; Fleming, William; Bagby, Grover C.; Grompe, Markus.

In: Blood, Vol. 116, No. 24, 09.12.2010, p. 5140-5148.

Research output: Contribution to journalArticle

Zhang, Q-S, Marquez-Loza, L, Eaton, L, Duncan, AW, Goldman, D, Anur, P, Watanabe-Smith, K, Rathbun, RK, Fleming, W, Bagby, GC & Grompe, M 2010, 'Fancd2-/- mice have hematopoietic defects that can be partially corrected by resveratrol', Blood, vol. 116, no. 24, pp. 5140-5148. https://doi.org/10.1182/blood-2010-04-278226
Zhang, Qing-Shuo ; Marquez-Loza, Laura ; Eaton, Laura ; Duncan, Andrew W. ; Goldman, Devorah ; Anur, Praveen ; Watanabe-Smith, Kevin ; Rathbun, R. Keaney ; Fleming, William ; Bagby, Grover C. ; Grompe, Markus. / Fancd2-/- mice have hematopoietic defects that can be partially corrected by resveratrol. In: Blood. 2010 ; Vol. 116, No. 24. pp. 5140-5148.
@article{62982eedb8504f69b1f0ff86d6a0f261,
title = "Fancd2-/- mice have hematopoietic defects that can be partially corrected by resveratrol",
abstract = "Progressive bone marrow failure is a major cause of morbidity and mortality in human Fanconi Anemia patients. In an effort to develop a Fanconi Anemia murine model to study bone marrow failure, we found that Fancd2-/- mice have readily measurable hematopoietic defects. Fancd2 deficiency was associated with a significant decline in the size of the c-Kit +Sca-1+Lineage- (KSL) pool and reduced stem cell repopulation and spleen colony-forming capacity. Fancd2-/- KSL cells showed an abnormal cell cycle status and loss of quiescence. In addition, the supportive function of the marrow microenvironment was compromised in Fancd2-/- mice. Treatment with Sirt1-mimetic and the antioxidant drug, resveratrol, maintained Fancd2-/- KSL cells in quiescence, improved the marrow micro-environment, partially corrected the abnormal cell cycle status, and significantly improved the spleen colony-forming capacity of Fancd2-/- bone marrow cells. We conclude that Fancd2-/- mice have readily quantifiable hematopoietic defects, and that this model is well suited for pharmacologic screening studies.",
author = "Qing-Shuo Zhang and Laura Marquez-Loza and Laura Eaton and Duncan, {Andrew W.} and Devorah Goldman and Praveen Anur and Kevin Watanabe-Smith and Rathbun, {R. Keaney} and William Fleming and Bagby, {Grover C.} and Markus Grompe",
year = "2010",
month = "12",
day = "9",
doi = "10.1182/blood-2010-04-278226",
language = "English (US)",
volume = "116",
pages = "5140--5148",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "24",

}

TY - JOUR

T1 - Fancd2-/- mice have hematopoietic defects that can be partially corrected by resveratrol

AU - Zhang, Qing-Shuo

AU - Marquez-Loza, Laura

AU - Eaton, Laura

AU - Duncan, Andrew W.

AU - Goldman, Devorah

AU - Anur, Praveen

AU - Watanabe-Smith, Kevin

AU - Rathbun, R. Keaney

AU - Fleming, William

AU - Bagby, Grover C.

AU - Grompe, Markus

PY - 2010/12/9

Y1 - 2010/12/9

N2 - Progressive bone marrow failure is a major cause of morbidity and mortality in human Fanconi Anemia patients. In an effort to develop a Fanconi Anemia murine model to study bone marrow failure, we found that Fancd2-/- mice have readily measurable hematopoietic defects. Fancd2 deficiency was associated with a significant decline in the size of the c-Kit +Sca-1+Lineage- (KSL) pool and reduced stem cell repopulation and spleen colony-forming capacity. Fancd2-/- KSL cells showed an abnormal cell cycle status and loss of quiescence. In addition, the supportive function of the marrow microenvironment was compromised in Fancd2-/- mice. Treatment with Sirt1-mimetic and the antioxidant drug, resveratrol, maintained Fancd2-/- KSL cells in quiescence, improved the marrow micro-environment, partially corrected the abnormal cell cycle status, and significantly improved the spleen colony-forming capacity of Fancd2-/- bone marrow cells. We conclude that Fancd2-/- mice have readily quantifiable hematopoietic defects, and that this model is well suited for pharmacologic screening studies.

AB - Progressive bone marrow failure is a major cause of morbidity and mortality in human Fanconi Anemia patients. In an effort to develop a Fanconi Anemia murine model to study bone marrow failure, we found that Fancd2-/- mice have readily measurable hematopoietic defects. Fancd2 deficiency was associated with a significant decline in the size of the c-Kit +Sca-1+Lineage- (KSL) pool and reduced stem cell repopulation and spleen colony-forming capacity. Fancd2-/- KSL cells showed an abnormal cell cycle status and loss of quiescence. In addition, the supportive function of the marrow microenvironment was compromised in Fancd2-/- mice. Treatment with Sirt1-mimetic and the antioxidant drug, resveratrol, maintained Fancd2-/- KSL cells in quiescence, improved the marrow micro-environment, partially corrected the abnormal cell cycle status, and significantly improved the spleen colony-forming capacity of Fancd2-/- bone marrow cells. We conclude that Fancd2-/- mice have readily quantifiable hematopoietic defects, and that this model is well suited for pharmacologic screening studies.

UR - http://www.scopus.com/inward/record.url?scp=78650042041&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650042041&partnerID=8YFLogxK

U2 - 10.1182/blood-2010-04-278226

DO - 10.1182/blood-2010-04-278226

M3 - Article

VL - 116

SP - 5140

EP - 5148

JO - Blood

JF - Blood

SN - 0006-4971

IS - 24

ER -