Evidence map›Paper›PMID 36366891›Full record

ArticleMolecular systems biology2022

Synthetic gene circuits for cell state detection and protein tuning in human pluripotent stem cells.

Laura Prochazka, Yale S Michaels, Charles Lau, Ross D Jones, Mona Siu, Ting Yin, Diana Wu, Esther Jang, Mercedes Vázquez-Cantú, Penney M Gilbert and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular systems biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

11 citing papers in PubMed, 15 citations in OpenAlex.

  1. From genes to germ layers: virtual twins of gastruloids.NPJ systems biology and applications · 2026
    Review
  2. Reimagining the Synthetic Biology DBTL Cycle with Machine Learning.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
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

13 authors at 4 institutions in 4 countries.

Laura ProchazkaInstitute of Biomedical Engineering (BME), University of Toronto, Toronto, ON, Canada.
Yale S MichaelsMichael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.ORCID 0000-0002-6857-5922
Charles LauInstitute of Biomedical Engineering (BME), University of Toronto, Toronto, ON, Canada.
Ross D JonesMichael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.
Mona SiuMichael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.
Ting YinInstitute of Biomedical Engineering (BME), University of Toronto, Toronto, ON, Canada.
Diana WuInstitute of Biomedical Engineering (BME), University of Toronto, Toronto, ON, Canada.
Esther JangInstitute of Biomedical Engineering (BME), University of Toronto, Toronto, ON, Canada.
Mercedes Vázquez-CantúInstitute of Biomedical Engineering (BME), University of Toronto, Toronto, ON, Canada.
Penney M GilbertInstitute of Biomedical Engineering (BME), University of Toronto, Toronto, ON, Canada.ORCID 0000-0001-5509-9616
Himanshu KaulSchool of Engineering, University of Leicester, Leicester, UK.ORCID 0000-0003-1586-7486
Yaakov BenensonSwiss Federal Institute of Technology (ETH) Zürich, Department of Biosystems Science and Engineering (D-BSSE), Basel, Switzerland.ORCID 0000-0003-1880-6507
Peter W ZandstraMichael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.ORCID 0000-0002-9568-733X
University of Toronto · CAUniversity of British Columbia · CAETH Zurich · CHUniversity of Leicester · GB

Funding

CIHR BPF 170702CIHR MOP 57885
6 · The paper itself

Abstract

During development, cell state transitions are coordinated through changes in the identity of molecular regulators in a cell type- and dose-specific manner. The ability to rationally engineer such transitions in human pluripotent stem cells (hPSC) will enable numerous applications in regenerative medicine. Herein, we report the generation of synthetic gene circuits that can detect a desired cell state using AND-like logic integration of endogenous miRNAs (classifiers) and, upon detection, produce fine-tuned levels of output proteins using an miRNA-mediated output fine-tuning technology (miSFITs). Specifically, we created an "hPSC ON" circuit using a model-guided miRNA selection and circuit optimization approach. The circuit demonstrates robust PSC-specific detection and graded output protein production. Next, we used an empirical approach to create an "hPSC-Off" circuit. This circuit was applied to regulate the secretion of endogenous BMP4 in a state-specific and fine-tuned manner to control the composition of differentiating hPSCs. Our work provides a platform for customized cell state-specific control of desired physiological factors in hPSC, laying the foundation for programming cell compositions in hPSC-derived tissues and beyond.

Indexed as

MicroRNAsPluripotent Stem CellsCell DifferentiationGene Regulatory NetworksGenes, SyntheticHumansProteinsMicroRNAsProteinscell fate controlclassificationhuman pluripotent stem cellsprotein tuningsynthetic gene circuits

Identifiers

PMID36366891
PMCPMC9650275
OpenAlexW4308913774

What OpenQuestion 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 OpenQuestion graph.