Aging-associated decrease in the histone acetyltransferase KAT6B is linked to altered hematopoietic stem cell differentiation
Open accessPublished version of a preprint
Abstract
Aged hematopoietic stem cells (HSCs) undergo biased lineage priming and differentiation toward production of myeloid cells. A comprehensive understanding of gene regulatory mechanisms causing HSC aging is needed to devise new strategies to sustainably improve immune function in aged individuals. Here, a focused short hairpin RNA screen of epigenetic factors reveals that the histone acetyltransferase Kat6b regulates myeloid cell production from hematopoietic progenitor cells. Within the stem and progenitor cell compartment, Kat6b is highly expressed in long-term (LT)-HSCs and is significantly decreased with aging at the transcript and protein levels. Knockdown of Kat6b in young LT-HSCs causes skewed production of myeloid cells at the expense of erythroid cells both in vitro and in vivo. Transcriptome analysis identifies enrichment of aging and macrophage-associated gene signatures alongside reduced expression of self-renewal and multilineage priming signatures. Together, our work identifies KAT6B as a novel epigenetic regulator of hematopoietic differentiation and a target to improve aged immune function.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The lysine acetyltransferase KAT6B, whose expression declines with age, is important for maintaining a youthful HSC differentiation profile.
“In addition, the lysine acetyltransferase KAT6B, whose expression declines with age, is important for maintaining a youthful HSC differentiation profile101.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [101]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 43 · Cited by 26
Research works printed but not linked: 1
- Gasteiger R, Janiga G, Stucht D, Hennemuth A, Friman O, Speck O, Markl M, Preim B. 2016 An Aging World: 2015, International Population Reports. doi: 10.1007/978-3-642-193354_63 · DOI
- Authors
- Khokhar, E. S., Borikar, S., Eudy, E., Stearns, T., Young, K., & Trowbridge, J. J.
- Affiliations
- Jackson Laboratory (US)
- Corresponding author
- Trowbridge, Jennifer J.
- Venue
- Experimental Hematology
- Publisher
- Elsevier BV
- Published
- 2020-02
- Volume
- 82
- Pages
- 43-52.e4
- ISSN
- 0301-472X (ISSN-L)
- PMC
- PMC7179256
- OpenAlex
- W3003709618
- Cited by
- 26
- References
- 43
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2023: 5 · 2022: 1 · 2021: 7 · 2020: 5
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Experimental Hematology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- National Institute on Aging
- National Institute of Diabetes and Digestive and Kidney Diseases
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- KAT6B, histone acetyltransferase, hematopoietic stem cell aging, hematopoietic stem cells, myeloid differentiation, lineage priming, hematopoietic progenitor cells, epigenetic regulation, self-renewal, erythroid cells
- MeSH terms
- Aging, Animals, Cell Differentiation, Male, Mice, Transgenic, Gene Expression Regulation, Enzymologic, Gene Expression Profiling, Myeloid Progenitor Cells, Erythroid Cells, Epigenesis, Genetic, Mice, Histone Acetyltransferases, Gene Knockout Techniques, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
