Evidence map›Paper›PMID 27934856›Full record

ArticleNature communications2016

Bulk cell density and Wnt/TGFbeta signalling regulate mesendodermal patterning of human pluripotent stem cells.

Henning Kempf, Ruth Olmer, Alexandra Haase, Annika Franke, Emiliano Bolesani, Kristin Schwanke, Diana Robles-Diaz, Michelle Coffee, Gudrun Göhring, Gerald Dräger and 7 more

Abstract read
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.

0numbers the graph read from it
0cells of the map it votes in
78citing 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

78 citing papers in PubMed.

  1. Review
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  7. Review
  8. Optogenetic Rescue Reveals Spatiotemporal Rules of Germ-Layer Patterning.bioRxiv : the preprint server for biology · 2025
    Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
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  18. Article
  19. A Possible Role of Tetrodotoxin-Sensitive NaInternational journal of molecular sciences · 2024
    Article
  20. Article

18 more citing papers are in PubMed but not listed here.

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

17 authors.

Henning KempfLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Hannover Medical School, 30625 Hannover, Germany.
Ruth OlmerLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Hannover Medical School, 30625 Hannover, Germany.
Alexandra HaaseLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Hannover Medical School, 30625 Hannover, Germany.
Annika FrankeLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Hannover Medical School, 30625 Hannover, Germany.
Emiliano BolesaniLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Hannover Medical School, 30625 Hannover, Germany.
Kristin SchwankeLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Hannover Medical School, 30625 Hannover, Germany.
Diana Robles-DiazLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Hannover Medical School, 30625 Hannover, Germany.
Michelle CoffeeLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Hannover Medical School, 30625 Hannover, Germany.
Gudrun GöhringREBIRTH-Cluster of Excellence, Hannover Medical School, 30625 Hannover, Germany.
Gerald DrägerREBIRTH-Cluster of Excellence, Hannover Medical School, 30625 Hannover, Germany.
Oliver PötzNatural and Medical Sciences Institute at the University of Tuebingen (NMI), 72770 Reutlingen, Germany.
Thomas JoosNatural and Medical Sciences Institute at the University of Tuebingen (NMI), 72770 Reutlingen, Germany.
Erik Martinez-HackertDepartment of Biochemistry and Molecular Biology, Michigan State University, 48824-1319 Michigan, USA.
Axel HaverichLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Hannover Medical School, 30625 Hannover, Germany.
Falk F R BuettnerREBIRTH-Cluster of Excellence, Hannover Medical School, 30625 Hannover, Germany.
Ulrich MartinLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Hannover Medical School, 30625 Hannover, Germany.
Robert ZweigerdtLeibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), Hannover Medical School, 30625 Hannover, Germany.ORCID http://orcid.org/0000-0002-4656-0770

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In vitro differentiation of human pluripotent stem cells (hPSCs) recapitulates early aspects of human embryogenesis, but the underlying processes are poorly understood and controlled. Here we show that modulating the bulk cell density (BCD: cell number per culture volume) deterministically alters anteroposterior patterning of primitive streak (PS)-like priming. The BCD in conjunction with the chemical WNT pathway activator CHIR99021 results in distinct paracrine microenvironments codifying hPSCs towards definitive endoderm, precardiac or presomitic mesoderm within the first 24 h of differentiation, respectively. Global gene expression and secretome analysis reveals that TGFß superfamily members, antagonist of Nodal signalling LEFTY1 and CER1, are paracrine determinants restricting PS progression. These data result in a tangible model disclosing how hPSC-released factors deflect CHIR99021-induced lineage commitment over time. By demonstrating a decisive, functional role of the BCD, we show its utility as a method to control lineage-specific differentiation. Furthermore, these findings have profound consequences for inter-experimental comparability, reproducibility, bioprocess optimization and scale-up.

Indexed as

Cell CountGene Expression RegulationHumansOligonucleotide Array Sequence AnalysisPluripotent Stem CellsProtein Array AnalysisPyridinesPyrimidinesRNA, Small InterferingSignal TransductionTranscriptomeTransforming Growth Factor betaWnt ProteinsChir 99021PyridinesPyrimidinesRNA, Small InterferingTransforming Growth Factor betaWnt Proteins

Identifiers

PMID27934856
PMCPMC5155150

What OpenQuestion holds

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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.