Cited by 567Hematopoietic Stem Cell TransplantationMesenchymal stem cell researchAcute Myeloid Leukemia Research

Cdc42 activity regulates hematopoietic stem cell aging and rejuvenation

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Florian, Maria Carolina, Dörr, Karin, Niebel, Anja, Daria, Deidre, Schrezenmeier, Hubert, Rojewski, Markus, Filippi, Marie-Dominique, Hasenberg, Anja +4 more·2012·Cell Stem Cell

Abstract

The decline in hematopoietic function seen during aging involves a progressive reduction in the immune response and an increased incidence of myeloid malignancy, and has been linked to aging of hematopoietic stem cells (HSCs). The molecular mechanisms underlying HSC aging remain unclear. Here we demonstrate that elevated activity of the small RhoGTPase Cdc42 in aged HSCs is causally linked to HSC aging and correlates with a loss of polarity in aged HSCs. Pharmacological inhibition of Cdc42 activity functionally rejuvenates aged HSCs, increases the percentage of polarized cells in an aged HSC population, and restores the level and spatial distribution of histone H4 lysine 16 acetylation to a status similar to that seen in young HSCs. Our data therefore suggest a mechanistic role for Cdc42 activity in HSC biology and epigenetic regulation, and identify Cdc42 activity as a pharmacological target for ameliorating stem cell aging.

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Crossref · 10.1016/j.stem.2012.04.007

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  • Low levels of p57 upon aging were also detected in aged hematopoietic stem cells.

    “low levels of p57 upon aging were also detected in aged hematopoietic stem cells (Florian et al., 2012).”

    From Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells (2017) · cites this paper as Florian et al., 2012

  • Pharmacologic inhibition of Cdc42 with a selective Cdc42 activity inhibitor rejuvenated hematopoietic stem cells.

    “For example, pharmacologic inhibition of Cdc42, a small Rho GTPase whose increased expression has been linked to murine HSC aging, with a selective Cdc42 activity inhibitor rejuvenated HSCs (95)”

    From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [95]

  • Aged HSCs show increased cell number, possibly due to reduced capacity for asymmetric division.

    “Regulation of cell number and cycling activity is different for aging HSCs, which actually show increases in cell number, possibly due to a reduced capacity for asymmetric division123, with no difference in cycling activity124.”

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Research works printed but not linked: 1

  1. Silva H Conboy IM StemBook Aging and stem cell renewal The Stem Cell Research Community 2008 20614587

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Authors
Florian, M. C., Dörr, K., Niebel, A., Daria, D., Schrezenmeier, H., Rojewski, M., Filippi, M.-D., Hasenberg, A., Gunzer, M., Scharffetter-Kochanek, K., Zheng, Y., & Geiger, H.
Affiliations
  • Universität Ulm (DE)
  • Cincinnati Children's Hospital Medical Center (US)
  • University of Duisburg-Essen (DE)
Corresponding author
Geiger, Hartmut
Venue
Cell Stem Cell
Publisher
Elsevier BV
Published
2012-05
Volume
10
Issue
5
Pages
520-530
ISSN
  • 1875-9777 (ISSN-L)
  • 1934-5909
OpenAlex
W2045024858
Cited by
564
References
55
Citations by year
2026: 25 · 2025: 43 · 2024: 52 · 2023: 36 · 2022: 29 · 2021: 69 · 2020: 48 · 2019: 41 · 2018: 58 · 2017: 35 · 2016: 44 · 2015: 24 · 2014: 27 · 2013: 28 · 2012: 4
FWCI
17.67
Type
journal article
Language
en
Open access
Locations
  • Cell stem cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (AG040118, R01AG040118)
  • National Heart, Lung, and Blood Institute (R01HL076604, HL076604)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK077762, R21DK077762)
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
Keywords
Cdc42, hematopoietic stem cells, stem cell aging, Rho GTPases, cell polarity, H4K16ac, epigenetic regulation, pharmacological inhibition, immunosenescence, myeloid neoplasms
MeSH terms
Acetylation, Animals, Cells, Cultured, Hematopoiesis, Hematopoietic Stem Cells, Histones, Rejuvenation, Tubulin, Cell Polarity, Cellular Senescence, Mice, Knockout, Aging, Premature, GTPase-Activating Proteins, cdc42 GTP-Binding Protein, Protein Transport, Myeloid Cells, Mice

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