Aging-like Phenotype and Defective Lineage Specification in SIRT1-Deleted Hematopoietic Stem and Progenitor Cells

Aging hematopoietic stem cells (HSCs) exhibit defective lineage specification that is thought to be central to increased incidence of myeloid malignancies and compromised immune competence in the elderly. Mechanisms underlying these age-related defects remain largely unknown. We show that the deacet...

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Main Authors:	Rimmelé, Pauline, Bigarella, Carolina L., Liang, Raymond, Izac, Brigitte, Dieguez-Gonzalez, Rebeca, Barbet, Gaetan, Donovan, Michael, Brugnara, Carlo, Blander, Julie M., Sinclair, David A., Ghaffari, Saghi
Format:	Online
Language:	English
Published:	Elsevier 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110778/

id	pubmed-4110778
recordtype	oai_dc
spelling	pubmed-41107782014-07-25 Aging-like Phenotype and Defective Lineage Specification in SIRT1-Deleted Hematopoietic Stem and Progenitor Cells Rimmelé, Pauline Bigarella, Carolina L. Liang, Raymond Izac, Brigitte Dieguez-Gonzalez, Rebeca Barbet, Gaetan Donovan, Michael Brugnara, Carlo Blander, Julie M. Sinclair, David A. Ghaffari, Saghi Article Aging hematopoietic stem cells (HSCs) exhibit defective lineage specification that is thought to be central to increased incidence of myeloid malignancies and compromised immune competence in the elderly. Mechanisms underlying these age-related defects remain largely unknown. We show that the deacetylase Sirtuin (SIRT)1 is required for homeostatic HSC maintenance. Differentiation of young SIRT1-deleted HSCs is skewed toward myeloid lineage associated with a significant decline in the lymphoid compartment, anemia, and altered expression of associated genes. Combined with HSC accumulation of damaged DNA and expression patterns of age-linked molecules, these have striking overlaps with aged HSCs. We further show that SIRT1 controls HSC homeostasis via the longevity transcription factor FOXO3. These findings suggest that SIRT1 is essential for HSC homeostasis and lineage specification. They also indicate that SIRT1 might contribute to delaying HSC aging. Elsevier 2014-06-06 /pmc/articles/PMC4110778/ /pubmed/25068121 http://dx.doi.org/10.1016/j.stemcr.2014.04.015 Text en © 2014 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Rimmelé, Pauline Bigarella, Carolina L. Liang, Raymond Izac, Brigitte Dieguez-Gonzalez, Rebeca Barbet, Gaetan Donovan, Michael Brugnara, Carlo Blander, Julie M. Sinclair, David A. Ghaffari, Saghi
spellingShingle	Rimmelé, Pauline Bigarella, Carolina L. Liang, Raymond Izac, Brigitte Dieguez-Gonzalez, Rebeca Barbet, Gaetan Donovan, Michael Brugnara, Carlo Blander, Julie M. Sinclair, David A. Ghaffari, Saghi Aging-like Phenotype and Defective Lineage Specification in SIRT1-Deleted Hematopoietic Stem and Progenitor Cells
author_facet	Rimmelé, Pauline Bigarella, Carolina L. Liang, Raymond Izac, Brigitte Dieguez-Gonzalez, Rebeca Barbet, Gaetan Donovan, Michael Brugnara, Carlo Blander, Julie M. Sinclair, David A. Ghaffari, Saghi
author_sort	Rimmelé, Pauline
title	Aging-like Phenotype and Defective Lineage Specification in SIRT1-Deleted Hematopoietic Stem and Progenitor Cells
title_short	Aging-like Phenotype and Defective Lineage Specification in SIRT1-Deleted Hematopoietic Stem and Progenitor Cells
title_full	Aging-like Phenotype and Defective Lineage Specification in SIRT1-Deleted Hematopoietic Stem and Progenitor Cells
title_fullStr	Aging-like Phenotype and Defective Lineage Specification in SIRT1-Deleted Hematopoietic Stem and Progenitor Cells
title_full_unstemmed	Aging-like Phenotype and Defective Lineage Specification in SIRT1-Deleted Hematopoietic Stem and Progenitor Cells
title_sort	aging-like phenotype and defective lineage specification in sirt1-deleted hematopoietic stem and progenitor cells
description	Aging hematopoietic stem cells (HSCs) exhibit defective lineage specification that is thought to be central to increased incidence of myeloid malignancies and compromised immune competence in the elderly. Mechanisms underlying these age-related defects remain largely unknown. We show that the deacetylase Sirtuin (SIRT)1 is required for homeostatic HSC maintenance. Differentiation of young SIRT1-deleted HSCs is skewed toward myeloid lineage associated with a significant decline in the lymphoid compartment, anemia, and altered expression of associated genes. Combined with HSC accumulation of damaged DNA and expression patterns of age-linked molecules, these have striking overlaps with aged HSCs. We further show that SIRT1 controls HSC homeostasis via the longevity transcription factor FOXO3. These findings suggest that SIRT1 is essential for HSC homeostasis and lineage specification. They also indicate that SIRT1 might contribute to delaying HSC aging.
publisher	Elsevier
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110778/
_version_	1613117886187962368

Aging-like Phenotype and Defective Lineage Specification in SIRT1-Deleted Hematopoietic Stem and Progenitor Cells

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