Evidence map›Paper›PMID 39880867›Full record

ArticleNature communications2025

Engineering synthetic signaling receptors to enable erythropoietin-free erythropoiesis.

Aadit P Shah, Kiran R Majeti, Freja K Ekman, Sridhar Selvaraj, Devesh Sharma, Roshani Sinha, Eric Soupene, Prathamesh Chati, Sofia E Luna, Carsten T Charlesworth and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Review
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

16 authors.

Aadit P Shah *School of Medicine, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-8672-6643
Kiran R Majeti *Department of Pediatrics, Stanford University, Stanford, CA, USA.
Freja K EkmanSchool of Medicine, Stanford University, Stanford, CA, USA.
Sridhar SelvarajDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
Devesh SharmaDepartment of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Roshani SinhaDepartment of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Eric SoupeneBenioff Children's Hospital Oakland, University of California, San Francisco, San Francisco, CA, USA.
Prathamesh ChatiDepartment of Biological & Medical Informatics, University of California, San Francisco, San Francisco, CA, USA.
Sofia E LunaSchool of Medicine, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-9173-9518
Carsten T CharlesworthDepartment of Genetics, Stanford University, Stanford, CA, USA.
Travis McCrearyDepartment of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Benjamin J LeschDepartment of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Tammy TranDepartment of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Simon N ChuDepartment of Surgery, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-3863-1548
Matthew H PorteusDepartment of Pediatrics, Stanford University, Stanford, CA, USA. mporteus@stanford.edu.ORCID http://orcid.org/0000-0002-3850-4648
M Kyle CromerDepartment of Surgery, University of California, San Francisco, San Francisco, CA, USA. kyle.cromer@ucsf.edu.ORCID http://orcid.org/0000-0002-8198-5010

Funding

Filling a Void of Research (FAVOR) Training for Transplant SurgeonsT32AI125222 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PETER G STOCK, Minnie M Sarwal · 2016 to 2026
$3.4M
American Society of Hematology (ASH) Minority Medical Student Award ProgramCalifornia Institute for Regenerative Medicine (CIRM) Bridges ProgramHertz Foundation (Fannie and John Hertz Foundation) FellowshipNational Science Foundation (NSF) Graduate Research Fellowship ProgramNIAID NIH HHS T32 AI125222Stanford University (SU) Knight-Hennessy ScholarshipStanford University (SU) Medical Scholars Research ProgramStanford University (SU) Medical Scientist Training ProgramUC | UC San Francisco | School of Pharmacy, University of California, San Francisco (UCSF School of Pharmacy) Mary Anne Koda-Kimble Seed Award for InnovationUC | UC San Francisco | UCSF Foundation Program for Breakthrough Biomedical Research: New Frontier Research AwardU.S. Department of Health & Human Services | National Institutes of Health (NIH) T32 Research Training in Transplant Surgery Fellowship (1T32AI125222-01)
6 · The paper itself

Abstract

Blood transfusion plays a vital role in modern medicine, but frequent shortages occur. Ex vivo manufacturing of red blood cells (RBCs) from universal donor cells offers a potential solution, yet the high cost of recombinant cytokines remains a barrier. Erythropoietin (EPO) signaling is crucial for RBC development, and EPO is among the most expensive media components. To address this challenge, we develop highly optimized small molecule-inducible synthetic EPO receptors (synEPORs) using design-build-test cycles and genome editing. By integrating synEPOR at the endogenous EPOR locus in O-negative induced pluripotent stem cells, we achieve equivalent erythroid differentiation, transcriptomic changes, and hemoglobin production using small molecules compared to EPO-supplemented cultures. This approach dramatically reduces culture media costs. Our strategy not only addresses RBC production challenges but also demonstrates how protein and genome engineering can introduce precisely regulated cellular behaviors, potentially improving scalable manufacturing of a wide range of clinically relevant cell types.

Indexed as

ErythropoiesisErythropoietinReceptors, ErythropoietinAnimalsCell DifferentiationErythrocytesGene EditingHemoglobinsHumansInduced Pluripotent Stem CellsMiceProtein EngineeringSignal TransductionErythropoietinHemoglobinsReceptors, Erythropoietin

Identifiers

PMID39880867
PMCPMC11779867

What Socratic holds

Textmetadata
LicenceCC BY
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.