Proliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell Compartment
Aging of the hematopoietic stem cell (HSC) compartment is characterized by lineage bias and reduced stem cell function, the molecular basis of which is largely unknown. Using single-cell transcriptomics, we identified a distinct subpopulation of old HSCs carrying a p53 signature indicative of stem c...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-05-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717306034 |
| _version_ | 1818062215510491136 |
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| author | Kristina Kirschner Tamir Chandra Vladimir Kiselev David Flores-Santa Cruz Iain C. Macaulay Hyun Jun Park Juan Li David G. Kent Rupa Kumar Dean C. Pask Tina L. Hamilton Martin Hemberg Wolf Reik Anthony R. Green |
| author_facet | Kristina Kirschner Tamir Chandra Vladimir Kiselev David Flores-Santa Cruz Iain C. Macaulay Hyun Jun Park Juan Li David G. Kent Rupa Kumar Dean C. Pask Tina L. Hamilton Martin Hemberg Wolf Reik Anthony R. Green |
| author_sort | Kristina Kirschner |
| collection | DOAJ |
| description | Aging of the hematopoietic stem cell (HSC) compartment is characterized by lineage bias and reduced stem cell function, the molecular basis of which is largely unknown. Using single-cell transcriptomics, we identified a distinct subpopulation of old HSCs carrying a p53 signature indicative of stem cell decline alongside pro-proliferative JAK/STAT signaling. To investigate the relationship between JAK/STAT and p53 signaling, we challenged HSCs with a constitutively active form of JAK2 (V617F) and observed an expansion of the p53-positive subpopulation in old mice. Our results reveal cellular heterogeneity in the onset of HSC aging and implicate a role for JAK2V617F-driven proliferation in the p53-mediated functional decline of old HSCs. |
| first_indexed | 2024-12-10T14:00:40Z |
| format | Article |
| id | doaj.art-8b76b64798534b639419288a43fe51f3 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T14:00:40Z |
| publishDate | 2017-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-8b76b64798534b639419288a43fe51f32022-12-22T01:45:49ZengElsevierCell Reports2211-12472017-05-011981503151110.1016/j.celrep.2017.04.074Proliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell CompartmentKristina Kirschner0Tamir Chandra1Vladimir Kiselev2David Flores-Santa Cruz3Iain C. Macaulay4Hyun Jun Park5Juan Li6David G. Kent7Rupa Kumar8Dean C. Pask9Tina L. Hamilton10Martin Hemberg11Wolf Reik12Anthony R. Green13Cambridge Institute for Medical Research, University of Cambridge, Cambridge, Cambridgeshire CB2 0XY, UKEpigenetics ISP, The Babraham Institute, Cambridge, Cambridgeshire CB22 3AT, UKThe Wellcome Trust Sanger Institute, Cambridge, Cambridgeshire CB10 1SA, UKCambridge Institute for Medical Research, University of Cambridge, Cambridge, Cambridgeshire CB2 0XY, UKThe Wellcome Trust Sanger Institute, Cambridge, Cambridgeshire CB10 1SA, UKCambridge Institute for Medical Research, University of Cambridge, Cambridge, Cambridgeshire CB2 0XY, UKCambridge Institute for Medical Research, University of Cambridge, Cambridge, Cambridgeshire CB2 0XY, UKCambridge Institute for Medical Research, University of Cambridge, Cambridge, Cambridgeshire CB2 0XY, UKCambridge Institute for Medical Research, University of Cambridge, Cambridge, Cambridgeshire CB2 0XY, UKCambridge Institute for Medical Research, University of Cambridge, Cambridge, Cambridgeshire CB2 0XY, UKCambridge Institute for Medical Research, University of Cambridge, Cambridge, Cambridgeshire CB2 0XY, UKThe Wellcome Trust Sanger Institute, Cambridge, Cambridgeshire CB10 1SA, UKEpigenetics ISP, The Babraham Institute, Cambridge, Cambridgeshire CB22 3AT, UKCambridge Institute for Medical Research, University of Cambridge, Cambridge, Cambridgeshire CB2 0XY, UKAging of the hematopoietic stem cell (HSC) compartment is characterized by lineage bias and reduced stem cell function, the molecular basis of which is largely unknown. Using single-cell transcriptomics, we identified a distinct subpopulation of old HSCs carrying a p53 signature indicative of stem cell decline alongside pro-proliferative JAK/STAT signaling. To investigate the relationship between JAK/STAT and p53 signaling, we challenged HSCs with a constitutively active form of JAK2 (V617F) and observed an expansion of the p53-positive subpopulation in old mice. Our results reveal cellular heterogeneity in the onset of HSC aging and implicate a role for JAK2V617F-driven proliferation in the p53-mediated functional decline of old HSCs.http://www.sciencedirect.com/science/article/pii/S2211124717306034agingscRNA-seqhematologyJAK2p53stem cellscellular agingcancerleukemiagenomics |
| spellingShingle | Kristina Kirschner Tamir Chandra Vladimir Kiselev David Flores-Santa Cruz Iain C. Macaulay Hyun Jun Park Juan Li David G. Kent Rupa Kumar Dean C. Pask Tina L. Hamilton Martin Hemberg Wolf Reik Anthony R. Green Proliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell Compartment Cell Reports aging scRNA-seq hematology JAK2 p53 stem cells cellular aging cancer leukemia genomics |
| title | Proliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell Compartment |
| title_full | Proliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell Compartment |
| title_fullStr | Proliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell Compartment |
| title_full_unstemmed | Proliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell Compartment |
| title_short | Proliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell Compartment |
| title_sort | proliferation drives aging related functional decline in a subpopulation of the hematopoietic stem cell compartment |
| topic | aging scRNA-seq hematology JAK2 p53 stem cells cellular aging cancer leukemia genomics |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717306034 |
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