Evidence map›Paper›PMID 41577693›Full record

ArticleNature communications2026

In vivo CRISPR screening identifies SAGA complex members as key regulators of hematopoiesis.

Archana Shankar, Leonid Olender, Ian Hsu, Masashi Miyauchi, Róbert Pálovics, Grace A Meaker, Satoshi Kaito, Ola Rizq, Hwei Minn Khoo, Yavor Bozhilov and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

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

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Archana Shankar *Graduate Program in Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-3499-4309
Leonid Olender *Department of Haematology, Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Ian HsuMRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Masashi MiyauchiInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-6301-3429
Róbert PálovicsWu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
Grace A MeakerMRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Satoshi KaitoThe Institute of Medical Science University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0001-7966-291X
Ola RizqThe Institute of Medical Science University of Tokyo, Tokyo, Japan.
Hwei Minn KhooMRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Yavor BozhilovDepartment of Haematology, Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Kyomi J IgarashiInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Joydeep BhaduryInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-4333-9974
Christy MunsonWu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
Paul K MackInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Tze-Kai TanGraduate Program in Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Jan RehwinkelMRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Atushi IwamaThe Institute of Medical Science University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0001-9410-8992
Tony Wyss-CorayWu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA. twc@stanford.edu.ORCID http://orcid.org/0000-0001-5893-0831
Hiromitsu NakauchiInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford University, Stanford, CA, USA. nakauchi@stanford.edu.ORCID http://orcid.org/0000-0002-9841-6973
Michael S HaneyWu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA. michael.haney@pennmedicine.upenn.edu.
Adam C WilkinsonDepartment of Haematology, Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK. acw63@cam.ac.uk.ORCID http://orcid.org/0000-0001-7406-0151

Funding

Training in Basic Research on Aging and Age-Related DiseaseT32AG000266 · NIA · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI Lisa M Ellerby · 1998 to 2026
$13.8M
Molecular signature of parabiosisR01AG072255 · NIA · STANFORD UNIVERSITY · PI WYSS-CORAY, TONY · 2021 to 2025
$2.4M
Modulating HSC-niche interactions to understand aging and improve transplantationR01HL147124 · NHLBI · STANFORD UNIVERSITY · PI NAKAUCHI, HIROMITSU · 2018 to 2021
$1.6M
Valine as a Metabolic Modulator of HematopoiesisR01DK116944 · NIDDK · STANFORD UNIVERSITY · PI NAKAUCHI, HIROMITSU · 2018 to 2021
$1.5M
A synthetic hematopoietic stem cell niche to investigate stemness and hematopathologiesK99HL150218 · NHLBI · STANFORD UNIVERSITY · PI WILKINSON, ADAM C · 2020 to 2020
$167k
European Hematology Association (EHA) RG-202211-02958Kay Kendall Leukaemia Fund (KKLF) KKL1378Leukemia and Lymphoma Society (Leukemia & Lymphoma Society) 3385-19NHLBI NIH HHS K99 HL150218NHLBI NIH HHS R01 HL147124NIA NIH HHS R01 AG072255NIA NIH HHS T32 AG000266NIDDK NIH HHS R01 DK116944U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) K99HL150218Wellcome TrustWellcome Trust (Wellcome) 302479Z23Z
6 · The paper itself

Abstract

The biological mechanisms that sustain the vast blood production required for healthy life remain incompletely understood. To search for cell intrinsic regulators of hematopoiesis, we perform a genome-wide in vivo hematopoietic stem and progenitor cell (HSPC)-based CRISPR knockout screen. We discover SAGA complex members, including Tada2b and Taf5l, as key regulators of hematopoiesis. Loss of Tada2b or Taf5l strongly inhibits hematopoiesis in vivo, causing a buildup of immature hematopoietic cells in the bone marrow. The SAGA complex deposits histone H3 lysine 9 acetylation (H3K9ac) and removes histone H2B ubiquitination (H2Bub). Loss of Tada2b leads to a reduction in H3K9ac levels and altered H2Bub enrichment in HSPCs, implicating disruption of SAGA complex activity. This is associated with upregulation of interferon pathway genes, reduced mitochondrial activity, and increased megakaryocyte progenitor cell commitment. Loss of these factors also enhances the cell outgrowth and the interferon pathway in an in vivo human myelodysplastic syndrome cell line model. In summary, this study identifies the SAGA complex as an important regulator of hematopoiesis.

Indexed as

HematopoiesisAcetylationAnimalsCRISPR-Cas SystemsHematopoietic Stem CellsHistonesHumansMiceMyelodysplastic SyndromesTATA-Binding Protein Associated FactorsUbiquitinationHistonesTATA-Binding Protein Associated Factors

Identifiers

PMID41577693
PMCPMC12914052

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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.