Evidence map›Paper›PMID 41889896›Full record

ArticlebioRxiv : the preprint server for biology2026

HAT1 Regulates Intestinal Stem Cell Proliferation and Differentiation.

Prabakaran Nagarajan, Caden J Martin, Andrea R Keller, Kübra B Akkaya-Colak, Maria H Festing, Maria M Mihaylova, Mark R Parthun

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Prabakaran NagarajanDepartment of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH 43210, USA.
Caden J MartinDepartment of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH 43210, USA.
Andrea R KellerDepartment of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH 43210, USA.
Kübra B Akkaya-ColakDepartment of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH 43210, USA.
Maria H FestingDepartment of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH 43210, USA.
Maria M MihaylovaDepartment of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH 43210, USA.
Mark R ParthunDepartment of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH 43210, USA.

Funding

Determining Age-Dependent Metabolic Changes in Tumors and Their MicroenvironmentDP2CA271361 · NCI · OHIO STATE UNIVERSITY · PI MIHAYLOVA, MARIA M. · 2021 to 2024
$2.3M
Histone Acetylation Dynamics and Epigenome DuplicationR01GM144601 · NIGMS · OHIO STATE UNIVERSITY · PI PARTHUN, MARK R · 2022 to 2025
$1.6M
NCI NIH HHS DP2 CA271361NIGMS NIH HHS R01 GM144601
6 · The paper itself

Abstract

Stem cells are critical for the development and maintenance of tissue integrity. An important example is intestinal stem cells (ISCs) that generate all epithelial cell types necessary for formation of the intestinal lining. HAT1, a histone acetyltransferase that acetylates newly synthesized histone H4 molecules on lysine residues 5 and 12 during replication-coupled chromatin assembly, is specifically expressed in intestinal stem and progenitor cells located in intestinal crypts. To determine if HAT1 is important for intestinal stem and progenitor cell function, we generated an inducible deletion of the HAT1 gene in intestinal epithelial cells. Loss of HAT1 resulted in morphological defects in the proximal end of the small intestine. Following loss of HAT1, intestinal crypts became elongated, with an increase in stem and progenitor cell proliferation and an increase in the population of OLFM+ cells. Loss of HAT1 also resulted in alterations in intestinal stem cell differentiation, including an increase in the number of Goblet cells and the mislocalization of Paneth cells into villi. HAT1 is specifically responsible for the acetylation of histone H4 lysine 5 (H4K5ac) in intestinal stem cells. Genome-wide characterization of HAT1-dependent H4K5ac in intestinal crypt cells indicates that the most significant loss of H4K5ac occurs in lamina-associated domains (LADs). Loss of H4K5ac in LADs is accompanied by an increase in histone H3 K9 tri-methylation indicating that HAT1 regulates LAD chromatin structure in intestinal crypt cells. A direct role for HAT1 in intestinal stem cell function was demonstrated using organoids in culture. HAT1 is required for differentiation in organoids and for the maintenance of Lgr5+ stem cells. These results indicate that HAT1 is required for the proper regulation of intestinal stem cell renewal and differentiation.

Identifiers

PMID41889896
PMCPMC13015452

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.