Evidence map›Paper›PMID 36657443›Full record

ArticleCell2023

Controlling organoid symmetry breaking uncovers an excitable system underlying human axial elongation.

Giridhar M Anand, Heitor C Megale, Sean H Murphy, Theresa Weis, Zuwan Lin, Yichun He, Xiao Wang, Jia Liu, Sharad Ramanathan

Open access · greenAbstract read
In one paragraph

Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
11.5field-weighted citation impact, top 1% 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

43 citing papers in PubMed, 75 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Organoids for disease modeling and treatment: state-of-the-art.Experimental hematology & oncology · 2026
    Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Bioengineering gradients for controlled embryo and organ modeling.Current opinion in biomedical engineering · 2025
    Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Bioengineering tools for next-generation neural organoids.Current opinion in neurobiology · 2025
    Review
  19. Article
  20. 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

9 authors at 2 institutions in 1 country.

Giridhar M AnandDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: ganand@g.harvard.edu.
Heitor C MegaleDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Sean H MurphyDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Theresa WeisDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Zuwan LinDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02138, USA.
Yichun HeSchool of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02138, USA.
Xiao WangBroad Institute of MIT and Harvard, Cambridge, MA 02138, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02138, USA.
Jia LiuSchool of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Sharad RamanathanDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: sharad@cgr.harvard.edu.
Harvard University · USBroad Institute · US

Funding

Measuring and modeling the dynamics ofpatterning in human stem cellsR01GM131105 · NIGMS · HARVARD UNIVERSITY · PI Sharad Ramanathan · 2019 to 2026
$2.9M
Determining lineage decisions and gene regulatory networks governing the generation of key progenitor cell types during early human brain developmentR01HD100036 · NICHD · HARVARD UNIVERSITY · PI RAMANATHAN, SHARAD · 2020 to 2024
$2.4M
"Building a robust organoid platform to study the developmental potential and physiology of human specific cortical cell types"RF1MH123948 · NIMH · HARVARD UNIVERSITY · PI LIU, JIA, RAMANATHAN, SHARAD · 2020 to 2020
$1.8M
NICHD NIH HHS R01 HD100036NIGMS NIH HHS R01 GM131105NIMH NIH HHS RF1 MH123948
6 · The paper itself

Abstract

The human embryo breaks symmetry to form the anterior-posterior axis of the body. As the embryo elongates along this axis, progenitors in the tail bud give rise to tissues that generate spinal cord, skeleton, and musculature. This raises the question of how the embryo achieves axial elongation and patterning. While ethics necessitate in vitro studies, the variability of organoid systems has hindered mechanistic insights. Here, we developed a bioengineering and machine learning framework that optimizes organoid symmetry breaking by tuning their spatial coupling. This framework enabled reproducible generation of axially elongating organoids, each possessing a tail bud and neural tube. We discovered that an excitable system composed of WNT/FGF signaling drives elongation by inducing a neuromesodermal progenitor-like signaling center. We discovered that instabilities in the excitable system are suppressed by secreted WNT inhibitors. Absence of these inhibitors led to ectopic tail buds and branches. Our results identify mechanisms governing stable human axial elongation.

Indexed as

Body PatterningMesodermEmbryo, MammalianHumansOrganoidsWnt Signaling Pathwayaxial elongationbioengineeringhuman stem cell modelsreproduciblestatistical inference

Identifiers

PMID36657443
PMCPMC10122509
OpenAlexW4317567753

What OpenQuestion holds

Textmetadata
LicenceTDM
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.