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...

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Autores principales: Kirschner, Kristina, Chandra, Tamir, Kiselev, Vladimir, Flores-Santa Cruz, David, Macaulay, Iain C., Park, Hyun Jun, Li, Juan, Kent, David G., Kumar, Rupa, Pask, Dean C., Hamilton, Tina L., Hemberg, Martin, Reik, Wolf, Green, Anthony R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2017
Materias:
Report
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457484/
https://www.ncbi.nlm.nih.gov/pubmed/28538171
http://dx.doi.org/10.1016/j.celrep.2017.04.074
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author Kirschner, Kristina
Chandra, Tamir
Kiselev, Vladimir
Flores-Santa Cruz, David
Macaulay, Iain C.
Park, Hyun Jun
Li, Juan
Kent, David G.
Kumar, Rupa
Pask, Dean C.
Hamilton, Tina L.
Hemberg, Martin
Reik, Wolf
Green, Anthony R.
author_facet Kirschner, Kristina
Chandra, Tamir
Kiselev, Vladimir
Flores-Santa Cruz, David
Macaulay, Iain C.
Park, Hyun Jun
Li, Juan
Kent, David G.
Kumar, Rupa
Pask, Dean C.
Hamilton, Tina L.
Hemberg, Martin
Reik, Wolf
Green, Anthony R.
author_sort Kirschner, Kristina
collection PubMed
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.
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spelling pubmed-54574842017-06-09 Proliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell Compartment Kirschner, Kristina Chandra, Tamir Kiselev, Vladimir Flores-Santa Cruz, David Macaulay, Iain C. Park, Hyun Jun Li, Juan Kent, David G. Kumar, Rupa Pask, Dean C. Hamilton, Tina L. Hemberg, Martin Reik, Wolf Green, Anthony R. Cell Rep Report 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. Cell Press 2017-05-23 /pmc/articles/PMC5457484/ /pubmed/28538171 http://dx.doi.org/10.1016/j.celrep.2017.04.074 Text en © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Report
Kirschner, Kristina
Chandra, Tamir
Kiselev, Vladimir
Flores-Santa Cruz, David
Macaulay, Iain C.
Park, Hyun Jun
Li, Juan
Kent, David G.
Kumar, Rupa
Pask, Dean C.
Hamilton, Tina L.
Hemberg, Martin
Reik, Wolf
Green, Anthony R.
Proliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell Compartment
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 Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457484/
https://www.ncbi.nlm.nih.gov/pubmed/28538171
http://dx.doi.org/10.1016/j.celrep.2017.04.074
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