# The role of PHF6 in the control of hematopoietic stem cell aging.

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $500,000

## Abstract

Project Summary/Abstract
As life expectancy increases age-associated pathologies have become a major health problem.
It is now recognized that stem cell aging is a driver of systemic and organ-specific functional
decline. In the hematopoietic system stem cell aging is characterized by accumulation of
immunophenotypically-defined hematopoietic stem cells (HSCs) with impaired self-renewal
capacity and altered differentiation programs with increased generation of myeloid populations
and decreased lymphoid potential. Here we show that genetic loss of Plant Homeodomain
Factor 6 (PHF6) results in increased HSC serial transplantation capacity and abrogates the
development of age-associated hematopoietic decay including the accumulation of functionally
exhausted HSCs displaying myeloid differentiation bias and impaired lymphoid potential. Our
central hypothesis is that loss of Phf6 reconfigures the epigenetic landscape of HSCs blocking
the initiation and/or progression of age-associated functional decline. Here we will apply the
combined expertise of the Ferrando and Rabadan labs in hematopoiesis and computational
biology to explore in depth the hematopoietic phenotypes and mechanisms of PHF6 inactivation
in HSC aging. Towards this goal we will analyze the stem cell compartment in Phf6 conditional
knockout mice and after CRISPR-directed PHF6 inactivation in human hematopoietic stem
cells, leveraging in vitro and in vivo stem cell assays in combination with advanced
computational analytical tools applied to single cell transcriptomics and epigenomics. These
studies will ultimately facilitate the development of new targeted therapies aimed at improving
the engraftment capacity of hematopoietic stem cells from aged donors and for the treatment of
pathologies resulting from age-associated HSC deterioration.

## Key facts

- **NIH application ID:** 10848421
- **Project number:** 5R01AG077020-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Teresa Palomero
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $500,000
- **Award type:** 5
- **Project period:** 2021-09-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10848421

## Citation

> US National Institutes of Health, RePORTER application 10848421, The role of PHF6 in the control of hematopoietic stem cell aging. (5R01AG077020-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10848421. Licensed CC0.

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