Evidence map›Paper›PMID 34937919›Full record

ArticleNature immunology2022

Identification of RIOK2 as a master regulator of human blood cell development.

Shrestha Ghosh, Mahesh Raundhal, Samuel A Myers, Steven A Carr, Xi Chen, Gregory A Petsko, Laurie H Glimcher

Abstract read
PubMed Publisher
In one paragraph

Article in Nature immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.6field-weighted citation impact, top 9% 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

13 citing papers in PubMed, 23 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 1 country.

Shrestha GhoshDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Mahesh RaundhalDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-8175-2957
Samuel A MyersBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Steven A CarrBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-7203-4299
Xi ChenDepartment of Molecular & Cellular Biology, Lester and Sue Smith Breast Center, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0002-7995-6202
Gregory A PetskoDepartment of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. gpetsko@bwh.harvard.edu.ORCID http://orcid.org/0000-0003-3668-3694
Laurie H GlimcherDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. laurie_glimcher@dfci.harvard.edu.ORCID http://orcid.org/0000-0002-4971-0404
Harvard University · USBroad Institute · USBaylor College of Medicine · USBrigham and Women's Hospital · US

Funding

MICROSCALED PROTEOGENOMICS FOR CANCER CLINICAL TRIALSU01CA214125 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ANURAG, MEENAKSHI, CARR, STEVEN A · 2017 to 2021
$7.0M
Center of Excellence for High Throughput Proteogenomic CharacterizationU24CA210986 · NCI · BROAD INSTITUTE, INC. · PI CARR, STEVEN A, GILLETTE, MICHAEL A · 2016 to 2020
$6.4M
Mechanism and Function of Endoplasmic Reticulum Protein Quality Control Machinery In The Maintenance of Hematopoietic Stem CellsR01HL146642 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI CHEN, XI · 2019 to 2023
$2.5M
Crosstalk Between the ER Stress Response and Mitochondrial Fatty Acid Oxidation in MYC-driven Breast CancerR37CA228304 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CHEN, XI · 2018 to 2024
$2.5M
Multi-faceted Roles of an Atypical Kinase RIOK2 in Erythropoiesis and Myelodyplastic SyndromesR03HL156574 · NHLBI · DANA-FARBER CANCER INST · PI GLIMCHER, LAURIE HOLLIS · 2020 to 2020
$177k
NCI NIH HHS R37 CA228304NCI NIH HHS U01 CA214125NCI NIH HHS U24 CA210986NHLBI NIH HHS R01 HL146642NHLBI NIH HHS R03 HL156574
6 · The paper itself

Abstract

Anemia is a major comorbidity in aging, chronic kidney and inflammatory diseases, and hematologic malignancies. However, the transcriptomic networks governing hematopoietic differentiation in blood cell development remain incompletely defined. Here we report that the atypical kinase RIOK2 (right open reading frame kinase 2) is a master transcription factor (TF) that not only drives erythroid differentiation, but also simultaneously suppresses megakaryopoiesis and myelopoiesis in primary human stem and progenitor cells. Our study reveals the previously uncharacterized winged helix-turn-helix DNA-binding domain and two transactivation domains of RIOK2 that are critical to regulate key hematopoietic TFs GATA1, GATA2, SPI1, RUNX3 and KLF1. This establishes RIOK2 as an integral component of the transcriptional regulatory network governing human hematopoietic differentiation. Importantly, RIOK2 mRNA expression significantly correlates with these TFs and other hematopoietic genes in myelodysplastic syndromes, acute myeloid leukemia and chronic kidney disease. Further investigation of RIOK2-mediated transcriptional pathways should yield therapeutic approaches to correct defective hematopoiesis in hematologic disorders.

Indexed as

Amino Acid SequenceBlood CellsCell DifferentiationCell Line, TumorCells, CulturedErythropoiesisGene Expression RegulationHEK293 CellsHematopoietic Stem CellsHumansK562 CellsLeukemia, Myeloid, AcuteMyelodysplastic SyndromesMyelopoiesisProtein Serine-Threonine KinasesTranscription FactorsProtein Serine-Threonine KinasesRIOK2 protein, humanTranscription Factors

Identifiers

PMID34937919
OpenAlexW4200445924

What OpenQuestion 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 OpenQuestion graph.