Evidence map›Paper›PMID 40000903›Full record

ArticleNature immunology2025

Transcriptional activation of regenerative hematopoiesis via microenvironmental sensing.

Tomer Itkin, Sean Houghton, Ryan Schreiner, Yang Lin, Chaitanya R Badwe, Veronique Voisin, Alex Murison, Negar Seyedhassantehrani, Kerstin B Kaufmann, Laura Garcia-Prat and 18 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Gut GABA keeps ILC3s in check.Nature immunology · 2025
    Article
  8. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

28 authors.

Tomer Itkin *Sagol Center for Regenerative Medicine, Department of Pathology, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel. tomitkin@tauex.tau.ac.il.ORCID http://orcid.org/0000-0002-9950-0149
Sean Houghton *Division of Regenerative Medicine, Hartman Institute for Therapeutic Organ Regeneration, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0001-6385-006X
Ryan SchreinerDivision of Regenerative Medicine, Hartman Institute for Therapeutic Organ Regeneration, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-7457-6606
Yang LinDivision of Regenerative Medicine, Hartman Institute for Therapeutic Organ Regeneration, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-0709-2468
Chaitanya R BadweDivision of Regenerative Medicine, Hartman Institute for Therapeutic Organ Regeneration, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Veronique VoisinPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Alex MurisonPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Negar SeyedhassantehraniNSF-CREST Center for Cellular and Biomolecular Machines, Department of Bioengineering, University of California, Merced, Merced, CA, USA.ORCID http://orcid.org/0009-0008-6718-615X
Kerstin B KaufmannPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0001-5013-6123
Laura Garcia-PratPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Gregory T BoothDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Fuqiang GengDivision of Regenerative Medicine, Hartman Institute for Therapeutic Organ Regeneration, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Ying LiuDivision of Regenerative Medicine, Hartman Institute for Therapeutic Organ Regeneration, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Jesus M Gomez-SalineroDivision of Regenerative Medicine, Hartman Institute for Therapeutic Organ Regeneration, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Jae-Hung ShiehDivision of Regenerative Medicine, Hartman Institute for Therapeutic Organ Regeneration, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
David RedmondDivision of Regenerative Medicine, Hartman Institute for Therapeutic Organ Regeneration, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-0983-8606
Jenny Z XiangGenomics Resources Core Facility, Weill Cornell Medicine, New York, NY, USA.
Steven Z JosefowiczImmunology and Microbial Pathogenesis Program, Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0001-7453-779X
Cole TrapnellDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-8105-4347
Eric M PietrasDivision of Hematology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.ORCID http://orcid.org/0000-0002-7339-8828
Joel A SpencerNSF-CREST Center for Cellular and Biomolecular Machines, Department of Bioengineering, University of California, Merced, Merced, CA, USA.ORCID http://orcid.org/0000-0002-4013-8763
Ross LevineHuman Oncology and Pathogenesis Program, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-7884-1905
Wenbin XiaoDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0001-8586-8500
Lior ZangiCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Brandon HadlandTranslational Science & Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
John E DickPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0002-9527-8317
Stephanie Z XiePrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0002-0284-494X
Shahin RafiiDivision of Regenerative Medicine, Hartman Institute for Therapeutic Organ Regeneration, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, New York, NY, USA. srafii@med.cornell.edu.ORCID http://orcid.org/0000-0001-5605-1067

Funding

The Memorial Sloan Kettering Cancer Center SPORE in LeukemiaP50CA254838 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Andriy Derkach · 2021 to 2026
$16.8M
Assessing lineage infidelity, oncogenic cooperativity and dependency in RUNX1-mutant acute myeloid leukemiaK08CA267058 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI XIAO, WENBIN · 2022 to 2025
$1.1M
NCI NIH HHS K08 CA267058NCI NIH HHS P50 CA254838
6 · The paper itself

Abstract

Transition between activation and quiescence states in hematopoietic stem and progenitor cells (HSPCs) is tightly governed by cell-intrinsic means and microenvironmental co-adaptation. Although this balance is fundamental for lifelong hematopoiesis and immunity, the underlying molecular mechanisms remain poorly defined. Multimodal analysis divulging differential transcriptional activity between distinct HSPC states indicates the presence of Fli-1 transcription factor binding motif in activated hematopoietic stem cells. We reveal that Fli-1 activity is essential during regenerative hematopoiesis in mice. Fli-1 directs activation programs while priming cellular sensory and output machineries, enabling HSPCs co-adoptability with a stimulated vascular niche through propagation of niche-derived angiocrine Notch1 signaling. Constitutively induced Notch1 signaling is sufficient to recuperate functional hematopoietic stem cells impairments in the absence of Fli-1, without leukemic transformation. Applying FLI-1 transient modified-mRNA transduction into latent adult human mobilized HSPCs, enables their niche-mediated expansion and superior engraftment capacities. Thus, decryption of stem cell activation programs offers valuable insights for immunological regenerative medicine.

Indexed as

HematopoiesisHematopoietic Stem CellsProto-Oncogene Protein c-fli-1RegenerationStem Cell NicheTranscriptional ActivationAnimalsHumansMiceMice, Inbred C57BLMice, KnockoutReceptor, Notch1Signal TransductionProto-Oncogene Protein c-fli-1Receptor, Notch1

Identifiers

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.