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| Status |
Public on Mar 06, 2013 |
| Title |
An Epigenetic Component of Hematopoietic Stem Cell Aging Amenable to Reprogramming Into a Young State |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Aging of hematopoietic stem cells (HSCs) leads to several functional changes, including alterations affecting self-renewal and differentiation. While it is well established that many of the age-induced changes are intrinsic to HSCs, less is known about the stability of this state. Here, we entertained the hypothesis that HSC aging is driven by the acquisition of permanent genetic mutations. To examine this issue at a functional level in vivo, we applied induced pluripotent stem (iPS) cell reprogramming of aged hematopoietic progenitors and allowed the resulting aged-derived iPS cells to reform hematopoiesis via blastocyst complementation. Next, we functionally characterized iPS-derived HSCs in primary chimeras and following the transplantation of 're-differentiated' HSCs into new hosts; the gold standard to assess HSC function. Our data demonstrate remarkably similar functional properties of iPS-derived and endogenous blastocyst-derived HSCs, despite the extensive chronological and proliferative age of the former. Our results therefore favor a model in which an underlying, but reversible, epigenetic component is a hallmark of HSC aging rather than being driven by an increased DNA mutation burden.
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| Overall design |
Hematopoietic stem cells (HSC) have been sorted out from young and aged steady-state mice, and from recipients transplanted with young and aged bone marrow. Generated iPS and commercially available ES cells were also sorted and analyzed.
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| Contributor(s) |
Wahlestedt M, Norddahl GL, Sten G, Ugale A, Frisk MM, Mattsson R, Deierborg T, Sigvardsson M, Bryder D |
| Citation(s) |
23476050, 28224997 |
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| Submission date |
Mar 06, 2013 |
| Last update date |
Sep 27, 2019 |
| Contact name |
Martin Wahlestedt |
| E-mail(s) |
martin.wahlestedt@med.lu.se
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| Organization name |
Lund University
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| Department |
Divison of Molecular Hematology
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| Street address |
Klinikgatan 26
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| City |
Lund |
| ZIP/Postal code |
22184 |
| Country |
Sweden |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (16)
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| GSM1093941 |
Young transplanted HSC, biological replicate 1 |
| GSM1093942 |
Young transplanted HSC, biological replicate 2 |
| GSM1093943 |
Aged transplanted HSC, biological replicate 1 |
| GSM1093944 |
Aged transplanted HSC, biological replicate 2 |
| GSM1093945 |
ES cells from Open Biosystems |
| GSM1093946 |
ES cells from Primogenix |
| GSM1093947 |
Aged steady-state male HSC, biological replicate 1 |
| GSM1093948 |
Aged steady-state male HSC, biological replicate 2 |
| GSM1093949 |
Aged steady-state male HSC, biological replicate 3 |
| GSM1093950 |
Young steady-state male HSC, biological replicate 1 |
| GSM1093951 |
Young steady-state male HSC, biological replicate 2 |
| GSM1093952 |
Young steady-state male HSC, biological replicate 3 |
| GSM1093953 |
iPS cells of a aged hematopoietic origin, biological replicate 1 |
| GSM1093954 |
iPS cells of a aged hematopoietic origin, biological replicate 2 |
| GSM1093955 |
iPS cells of a young hematopoietic origin, biological replicate 1 |
| GSM1093956 |
iPS cells of a young hematopoietic origin, biological replicate 2 |
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| Relations |
| BioProject |
PRJNA192530 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE44923_RAW.tar |
57.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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