Evidence map›Paper›PMID 36747813›Full record

ArticlebioRxiv : the preprint server for biology2023

Synthetic genetic circuits to uncover and enforce the OCT4 trajectories of successful reprogramming of human fibroblasts.

Katherine Ilia, Nika Shakiba, Trevor Bingham, Ross D Jones, Michael M Kaminski, Eliezer Aravera, Simone Bruno, Sebastian Palacios, Ron Weiss, James J Collins and 2 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed, 8 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 7 institutions in 5 countries.

Katherine IliaDepartment of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
Nika ShakibaDepartment of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
Trevor BinghamBoston Children's Hospital Stem Cell Program, Boston Children's Hospital, Boston, MA, 02115, USA.
Ross D JonesDepartment of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
Michael M KaminskiDepartment of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
Eliezer AraveraDepartment of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
Simone BrunoDepartment of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Sebastian PalaciosDepartment of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
Ron WeissDepartment of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
James J CollinsDepartment of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
Domitilla Del VecchioSynthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Thorsten M SchlaegerBoston Children's Hospital Stem Cell Program, Boston Children's Hospital, Boston, MA, 02115, USA.
Synthetic Biologics (United States) · USBoston Children's Hospital · USUniversity of British Columbia · CAApplied Science Private University · JOBroad Institute · USMassachusetts Institute of Technology · USMax Delbrück Center · DE

Funding

Synthetic Genetic Controller Circuits to Reprogram Cell FateR01EB024591 · NIBIB · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI COLLINS, JAMES J, DEL VECCHIO, DOMITILLA · 2017 to 2020
$2.5M
NIBIB NIH HHS R01 EB024591
6 · The paper itself

Abstract

Reprogramming human fibroblasts to induced pluripotent stem cells (iPSCs) is inefficient, with heterogeneity among transcription factor (TF) trajectories driving divergent cell states. Nevertheless, the impact of TF dynamics on reprogramming efficiency remains uncharted. Here, we identify the successful reprogramming trajectories of the core pluripotency TF, OCT4, and design a genetic controller that enforces such trajectories with high precision. By combining a genetic circuit that generates a wide range of OCT4 trajectories with live-cell imaging, we track OCT4 trajectories with clonal resolution and find that a distinct constant OCT4 trajectory is required for colony formation. We then develop a synthetic genetic circuit that yields a tight OCT4 distribution around the identified trajectory and outperforms in terms of reprogramming efficiency other circuits that less accurately regulate OCT4. Our synthetic biology approach is generalizable for identifying and enforcing TF dynamics for cell fate programming applications.

Identifiers

PMID36747813
PMCPMC9900859
OpenAlexW4318033678

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.