ArticleProceedings of the National Academy of Sciences of the United States of America2012
Predictive microfluidic control of regulatory ligand trajectories in individual pluripotent cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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.
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.
Who cites it
25 citing papers in PubMed, 72 citations in OpenAlex.
- Insights into human melanocyte development and characteristics through pluripotent stem cells combined with single-cell sequencing.iScience · 2025Article
- Macroscopic quorum sensing sustains differentiating embryonic stem cells.Nature chemical biology · 2023Article
- Pluripotent Stem Cell Platforms for Drug Discovery.Trends in molecular medicine · 2018Review
- Hydrodynamics in Cell Studies.Chemical reviews · 2018Review
- Modeling signaling-dependent pluripotency with Boolean logic to predict cell fate transitions.Molecular systems biology · 2018Article
- High-efficiency cellular reprogramming with microfluidics.Nature methods · 2016Article
- Advances in microfluidic platforms for analyzing and regulating human pluripotent stem cells.Current opinion in genetics & development · 2015Review
- Analysis of single-cell cytokine secretion reveals a role for paracrine signaling in coordinating macrophage responses to TLR4 stimulation.Science signaling · 2015Article
- Predictions for optimal mitigation of paracrine inhibitory signalling in haemopoietic stem cell cultures.Stem cell research & therapy · 2015Article
- A global assessment of stem cell engineering.Tissue engineering. Part A · 2014Article
- A method to recapitulate early embryonic spatial patterning in human embryonic stem cells.Nature methods · 2014Article
- Human pluripotent stem cell culture: considerations for maintenance, expansion, and therapeutics.Cell stem cell · 2014Review
- Concise review: microfluidic technology platforms: poised to accelerate development and translation of stem cell-derived therapies.Stem cells translational medicine · 2014Review
- Minireview: intraislet regulation of insulin secretion in humans.Molecular endocrinology (Baltimore, Md.) · 2013Review
- Engineering stem cell niches in bioreactors.World journal of stem cells · 2013Review
- Stochastic model-assisted development of efficient low-dose viral transduction in microfluidics.Biophysical journal · 2013Article
- Emerging strategies for spatiotemporal control of stem cell fate and morphogenesis.Trends in biotechnology · 2013Review
- Micro total analysis systems: fundamental advances and applications in the laboratory, clinic, and field.Analytical chemistry · 2013Review
- Toxicological effects of the different substances in tobacco smoke on human embryonic development by a systems chemo-biology approach.PloS one · 2013Article
- Spatial pattern dynamics of 3D stem cell loss of pluripotency via rules-based computational modeling.PLoS computational biology · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Local (cell-level) signaling environments, regulated by autocrine and paracrine signaling, and modulated by cell organization, are hypothesized to be fundamental stem cell fate control mechanisms used during development. It has, however, been challenging to demonstrate the impact of cell-level organization on stem cell fate control and to relate stem cell fate outcomes to autocrine and paracrine signaling. We address this fundamental problem using a combined in silico and experimental approach in which we directly manipulate, using laminar fluid flow, the local impact of endogenously secreted gp130-activating ligands and their activation of signal transducer and activator of transcription3 (STAT3) signaling in mouse embryonic stem cells (mESC). Our model analysis predicted that flow-dependent changes in autocrine and paracrine ligand binding would impact heterogeneity in cell- and colony-level STAT3 signaling activation and cause a gradient of cell fate determination along the direction of flow. Interestingly, analysis also predicted that local cell density would be inversely proportional to the degree to which endogenous secretion contributed to cell fate determination. Experimental validation using functional activation of STAT3 by secreted factors under microfluidic perfusion culture demonstrated that STAT3 activation and consequently mESC fate were manipulable by flow rate, position in the flow field, and local cell organization. As a unique demonstration of how quantitative control of autocrine and paracrine signaling can be integrated with spatial organization to elicit higher order cell fate effects, this work provides a general template to investigate organizing principles due to secreted factors.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.