Aging-like phenotype and defective lineage specification in SIRT1-deleted hematopoietic stem and progenitor cells.
Aging-like phenotype and defective lineage specification in SIRT1-deleted hematopoietic stem and progenitor cells.
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DOI：
10.1016/j.stemcr.2014.04.015
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发表时间：
2014-07-08
影响因子：
5.9
通讯作者：
Ghaffari, Saghi
中科院分区：
文献类型：
--
作者：
Rimmele, 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 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. SIRT1 deacetylase is essential for homeostatic maintenance of HSCs SIRT1 regulates HSC homeostasis via the longevity factor FOXO3 SIRT1 is essential for HSC lineage specification Young SIRT1-deleted HSCs have overlapping features with old HSCs SIRT1 deacetylase is essential for homeostatic maintenance of HSCs and for HSC lineage specification. Differentiation of young SIRT1-deleted HSCs is myeloid biased, defective in lymphoid cell production, leads to anemia, and recapitulates the main features of aged HSCs, suggesting that SIRT1 might contribute to delaying HSC aging. The longevity transcription factor FOXO3 mediates the SIRT1 effects on HSC homeostasis.
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影响因子：
8.8
作者：
Brown K;Xie S;Qiu X;Mohrin M;Shin J;Liu Y;Zhang D;Scadden DT;Chen D
通讯作者：
Chen D
影响因子：
23.9
作者：
Florian, Maria Carolina;Doerr, Karin;Niebel, Anja;Daria, Deidre;Schrezenmeier, Hubert;Rojewski, Markus;Filippi, Marie-Dominique;Hasenberg, Anja;Gunzer, Matthias;Scharffetter-Kochanek, Karin;Zheng, Yi;Geiger, Hartmut
通讯作者：
Geiger, Hartmut
DOI：
10.1083/jcb.201010131
发表时间：
2011-04-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Liu L;Rando TA
通讯作者：
Rando TA
影响因子：
4.4
作者：
Hinman, Rochelle M.;Nichols, Whitney A.;Satterthwaite, Anne B.
通讯作者：
Satterthwaite, Anne B.
DOI：
10.1084/jem.20111490
发表时间：
2011-12-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dykstra B;Olthof S;Schreuder J;Ritsema M;de Haan G
通讯作者：
de Haan G