Evidence map›Paper›PMID 33690842›Full record

ArticleBlood2021

The equilibrative nucleoside transporter ENT1 is critical for nucleotide homeostasis and optimal erythropoiesis.

Mahmoud Mikdar, Pedro González-Menéndez, Xiaoli Cai, Yujin Zhang, Marion Serra, Abdoul K Dembele, Anne-Claire Boschat, Sylvia Sanquer, Cerina Chhuon, Ida Chiara Guerrera and 10 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
8.0field-weighted citation impact, top 2% of its field
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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

24 citing papers in PubMed, 38 citations in OpenAlex.

  1. Review
  2. Autophagy · 2026
    Article
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  4. Article
  5. Review
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  18. Article
  19. Drug transport by red blood cells.Frontiers in physiology · 2023
    Review
  20. Inborn Errors of Nucleoside Transporter (NT)-Encoding Genes (International journal of molecular sciences · 2022
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 6 institutions in 2 countries.

Mahmoud MikdarUniversité de Paris, Unité Mixte de Recherche (UMR) S1134, Biologie Intégrée du Globule Rouge, INSERM, Paris, France.ORCID 0000-0003-3449-2851
Pedro González-MenéndezLaboratoire d'Excellence (GR-Ex), Paris, France.ORCID 0000-0003-3114-6304
Xiaoli CaiDepartment of Biochemistry and Molecular Biology, University of Texas McGovern Medical School at Houston, Houston, TX.
Yujin ZhangDepartment of Biochemistry and Molecular Biology, University of Texas McGovern Medical School at Houston, Houston, TX.
Marion SerraUniversité de Paris, Unité Mixte de Recherche (UMR) S1134, Biologie Intégrée du Globule Rouge, INSERM, Paris, France.
Abdoul K DembeleUniversité de Paris, Unité Mixte de Recherche (UMR) S1134, Biologie Intégrée du Globule Rouge, INSERM, Paris, France.
Anne-Claire BoschatPlateforme de Spectrométrie de Masse, Imagine Institute, Paris, France.ORCID 0000-0001-9535-9435
Sylvia SanquerINSERM UMR S1124, Université de Paris, Service de Biochimie Métabolomique et Protéomique, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
Cerina ChhuonUniversité de Paris, Proteomics Platform 3P5-Necker, Structure Fédérative de Recherche Necker, INSERM US24/CNRS, Paris, France.
Ida Chiara GuerreraUniversité de Paris, Proteomics Platform 3P5-Necker, Structure Fédérative de Recherche Necker, INSERM US24/CNRS, Paris, France.ORCID 0000-0002-4832-6793
Marc SitbonInstitut de Génétique Moléculaire de Montpellier, Universite Montpellier, Centre National de la Recherche Scientifique (CNRS), Montpellier, France.ORCID 0000-0003-3616-2338
Olivier HermineLaboratoire d'Excellence (GR-Ex), Paris, France.
Yves ColinUniversité de Paris, Unité Mixte de Recherche (UMR) S1134, Biologie Intégrée du Globule Rouge, INSERM, Paris, France.ORCID 0000-0001-5196-4254
Caroline Le Van KimUniversité de Paris, Unité Mixte de Recherche (UMR) S1134, Biologie Intégrée du Globule Rouge, INSERM, Paris, France.ORCID 0000-0002-3251-1310
Sandrina KinetLaboratoire d'Excellence (GR-Ex), Paris, France.
Narla MohandasNew York Blood Center, New York, NY; and.ORCID 0000-0003-2271-5296
Yang XiaDepartment of Biochemistry and Molecular Biology, University of Texas McGovern Medical School at Houston, Houston, TX.ORCID 0000-0002-8059-6179
Thierry PeyrardUniversité de Paris, Unité Mixte de Recherche (UMR) S1134, Biologie Intégrée du Globule Rouge, INSERM, Paris, France.ORCID 0000-0002-7715-568X
Naomi TaylorLaboratoire d'Excellence (GR-Ex), Paris, France.
Slim AzouziUniversité de Paris, Unité Mixte de Recherche (UMR) S1134, Biologie Intégrée du Globule Rouge, INSERM, Paris, France.ORCID 0000-0001-5519-4031
Centre National de la Recherche Scientifique · FRInserm · FRThe University of Texas Health Science Center at Houston · USHôpital Necker-Enfants Malades · FRInstitut des Maladies Génétiques Imagine · FRNew York Blood Center · US

Funding

YEAST MEMBRANE CYTOSKELETONP01DK032094 · NIDDK · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI NARLA, MOHANDAS · 1987 to 2021
$26.7M
Reprogramming hematopoietic stem cell (HSC) differentiation via metabolic conditZIABC011924 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI TAYLOR, NAOMI · 2019 to 2025
$9.0M
Erythrocyte metabolomic profiling reveals new insight and approaches to promote oxygen deliveryR01HL136969 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI PUTKEY, JOHN ANTHONY, ZHANG, YUJIN · 2017 to 2019
$1.5M
Molecular insight of erythrocyte hypoxic metabolic reprogramming in chronic kidney diseaseR01HL137990 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI XIA, YANG · 2017 to 2018
$989k
NHLBI NIH HHS R01 HL136969NHLBI NIH HHS R01 HL137990NIDDK NIH HHS P01 DK032094
6 · The paper itself

Abstract

The tight regulation of intracellular nucleotides is critical for the self-renewal and lineage specification of hematopoietic stem cells (HSCs). Nucleosides are major metabolite precursors for nucleotide biosynthesis and their availability in HSCs is dependent on their transport through specific membrane transporters. However, the role of nucleoside transporters in the differentiation of HSCs to the erythroid lineage and in red cell biology remains to be fully defined. Here, we show that the absence of the equilibrative nucleoside transporter (ENT1) in human red blood cells with a rare Augustine-null blood type is associated with macrocytosis, anisopoikilocytosis, an abnormal nucleotide metabolome, and deregulated protein phosphorylation. A specific role for ENT1 in human erythropoiesis was demonstrated by a defective erythropoiesis of human CD34+ progenitors following short hairpin RNA-mediated knockdown of ENT1. Furthermore, genetic deletion of ENT1 in mice was associated with reduced erythroid progenitors in the bone marrow, anemia, and macrocytosis. Mechanistically, we found that ENT1-mediated adenosine transport is critical for cyclic adenosine monophosphate homeostasis and the regulation of erythroid transcription factors. Notably, genetic investigation of 2 ENT1null individuals demonstrated a compensation by a loss-of-function variant in the ABCC4 cyclic nucleotide exporter. Indeed, pharmacological inhibition of ABCC4 in Ent1-/- mice rescued erythropoiesis. Overall, our results highlight the importance of ENT1-mediated nucleotide metabolism in erythropoiesis.

Indexed as

ErythropoiesisHomeostasisAdenosine MonophosphateAnimalsEquilibrative Nucleoside Transporter 1Hematopoietic Stem CellsHumansMiceMice, KnockoutAdenosine MonophosphateEquilibrative Nucleoside Transporter 1SLC29A1 protein, humanSLC29A1 protein, mouse

Identifiers

PMID33690842
PMCPMC8225918
OpenAlexW3134033695

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.