Functional dissection of the gene regulatory mechanism underlying variation in blood CD34+ cell levels at 1p36.23/ENO1
(2025) In Scientific Reports 16(1).- Abstract
Understanding the genetic regulation of blood CD34+ cell levels could lead to better methods for stem cell mobilization and transplantation. Recently, in a genome-wide association study (GWAS), we identified 11 genetic associations with blood CD34+ cell levels. One of the most significant maps to an intergenic region between the ENO1 and RERE genes at chromosome 1p36.23. However, the underlying mechanism remains unknown. Here, using functional fine-mapping, we identify rs10864368:C > T as a causal non-coding variant. Specifically, the rs10864368-T allele abrogates a binding site for the GATA2 transcription factor, leading to downregulation of ENO1 and RERE and lower CD34+ cell levels. Our data link a... (More)
Understanding the genetic regulation of blood CD34+ cell levels could lead to better methods for stem cell mobilization and transplantation. Recently, in a genome-wide association study (GWAS), we identified 11 genetic associations with blood CD34+ cell levels. One of the most significant maps to an intergenic region between the ENO1 and RERE genes at chromosome 1p36.23. However, the underlying mechanism remains unknown. Here, using functional fine-mapping, we identify rs10864368:C > T as a causal non-coding variant. Specifically, the rs10864368-T allele abrogates a binding site for the GATA2 transcription factor, leading to downregulation of ENO1 and RERE and lower CD34+ cell levels. Our data link a specific GATA2 target to the regulation of CD34+ cell levels, expanding on the role of GATA2 in human hematopoieisis.
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- author
- Ali, Zain LU ; Cafaro, Caterina LU ; Ekdahl, Ludvig LU ; Lamarca, Antton LU ; Lopez de Lapuente Portilla, Aitzkoa LU and Nilsson, Björn LU
- organization
-
- LUCC: Lund University Cancer Centre
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
- Division of Hematology and Clinical Immunology
- Hematogenomics (research group)
- Department of Laboratory Medicine
- Stem Cell Center
- Clinical Memory Research (research group)
- MultiPark: Multidisciplinary research on neurodegenerative diseases
- EpiHealth: Epidemiology for Health
- publishing date
- 2025-11-29
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Gata-2, Hematopoietic stem and progenitor cells, Stem cell transplantation
- in
- Scientific Reports
- volume
- 16
- issue
- 1
- article number
- 558
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:41318785
- scopus:105026898392
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-025-30068-4
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © The Author(s) 2025.
- id
- 646e0989-1903-4e0b-83a6-48476dfefec1
- date added to LUP
- 2026-03-09 16:50:01
- date last changed
- 2026-05-19 04:21:09
@article{646e0989-1903-4e0b-83a6-48476dfefec1,
abstract = {{<p>Understanding the genetic regulation of blood CD34<sup>+</sup> cell levels could lead to better methods for stem cell mobilization and transplantation. Recently, in a genome-wide association study (GWAS), we identified 11 genetic associations with blood CD34<sup>+</sup> cell levels. One of the most significant maps to an intergenic region between the ENO1 and RERE genes at chromosome 1p36.23. However, the underlying mechanism remains unknown. Here, using functional fine-mapping, we identify rs10864368:C > T as a causal non-coding variant. Specifically, the rs10864368-T allele abrogates a binding site for the GATA2 transcription factor, leading to downregulation of ENO1 and RERE and lower CD34<sup>+</sup> cell levels. Our data link a specific GATA2 target to the regulation of CD34<sup>+</sup> cell levels, expanding on the role of GATA2 in human hematopoieisis.</p>}},
author = {{Ali, Zain and Cafaro, Caterina and Ekdahl, Ludvig and Lamarca, Antton and Lopez de Lapuente Portilla, Aitzkoa and Nilsson, Björn}},
issn = {{2045-2322}},
keywords = {{Gata-2; Hematopoietic stem and progenitor cells; Stem cell transplantation}},
language = {{eng}},
month = {{11}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{Functional dissection of the gene regulatory mechanism underlying variation in blood CD34<sup>+</sup> cell levels at 1p36.23/ENO1}},
url = {{http://dx.doi.org/10.1038/s41598-025-30068-4}},
doi = {{10.1038/s41598-025-30068-4}},
volume = {{16}},
year = {{2025}},
}