Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 3 complete abstracts (436 words), 9 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Differentiation, Cell; Cell Differentiations; Differentiations, Cell.
Where it fits in the MeSH classification
- Broader topics
- Cell Physiological Phenomena
- Narrower topics
- Adipogenesis; Asymmetric Cell Division; Cellular Reprogramming; Embryonic Induction; Gametogenesis; Hematopoiesis; Neurogenesis
- See also
- Antigens, Differentiation; Cell Lineage
Research landscape
PubMed indexes 389,196 records tagged with the MeSH heading “Cell Differentiation” (counts retrieved 2026-10-29). 77,631 of them (19.9%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 132,082 records.
Reviews account for 55,844 records (14.3%) and meta-analyses for 256. Randomized controlled trials number 759 (0.2%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 96,588 |
| 2000-2009 | 82,895 |
| 2010-2019 | 132,082 |
| 2020 onward | 77,631 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 55,844 | 14.3% |
| Meta-analyses | 256 | 0.1% |
| Randomized controlled trials | 759 | 0.2% |
Method: PubMed query "Cell Differentiation"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in molecular biology
Molecular biology establishes mechanisms through controlled experiments, often in simplified systems such as purified proteins, cultured cells or model organisms. Such work can show what is possible in a defined system, but whether a pathway matters in a whole organism or in human disease needs further evidence. Check the experimental system, whether findings were reproduced by independent groups, and whether the authors tested the mechanism directly or inferred it from correlation.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Repetitive neuronal activation regulates cellular maturation state via nuclear reprogramming | 2026 | Research article Design not recorded in structured metadata | 5 | cc by PMID 42469214 · DOI · PMC13379389 |
| Reprogramming of host energy metabolism mediated by the TNF-iNOS-HIF-1α axis plays a key role in host resistance to Plasmodium infection | 2026 | Research article Design not recorded in structured metadata | 3 | cc by PMID 42506979 · DOI · PMC13405620 |
| ATP13A4 gates extracellular polyamine levels to control excitatory synaptogenesis | 2026 | Research article Design not recorded in structured metadata | 2 | cc by PMID 42680725 · DOI · PMC13534584 |
Repetitive neuronal activation regulates cellular maturation state via nuclear reprogramming [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Neural stimulation, such as electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS), is highly effective clinical intervention for a broad spectrum of psychiatric disorders, including depression and schizophrenia.
- Closing excerpt
- These findings demonstrate that chronically-repeated brain stimulation triggers plasticity of the cellular state, revealing a form of stimulus-regulated nuclear reprogramming with potential clinical utility.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (150 words)
Neural stimulation, such as electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS), is highly effective clinical intervention for a broad spectrum of psychiatric disorders, including depression and schizophrenia. However, their mechanism of action at the cellular level remains poorly understood. Here, we model ECT with repeated optogenetic neuronal stimulation in the mouse dentate gyrus, and observe ECT-relevant behavioral changes, including decreased depression-like behavior and increased locomotor activity. At the cellular level, we identify dematuration to a long-term stable state, persisting for more than one month, defined by changes in nuclear structure, gene expression patterns resembling the G2/M phase of the cell cycle, and altered neural coding of navigational information. Moreover, knockout of the G2/M master regulator Cyclin B attenuates some of behavioral and cellular effects. These findings demonstrate that chronically-repeated brain stimulation triggers plasticity of the cellular state, revealing a form of stimulus-regulated nuclear reprogramming with potential clinical utility.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42469214 · DOI · PMC13379389
Reprogramming of host energy metabolism mediated by the TNF-iNOS-HIF-1α axis plays a key role in host resistance to Plasmodium infection [2]
Abstract reading summary — source excerpts
- Opening excerpt
- TNF has a dual effect in Plasmodium infection, bolstering the host's immune defense while also inducing sickness behavior.
- Closing excerpt
- Altogether, our results indicate that TNF-iNOS-HIF-1α-induced glycolysis in monocytes plays a critical role in host defense and sickness behavior in Pc-infected mice.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (133 words)
TNF has a dual effect in Plasmodium infection, bolstering the host's immune defense while also inducing sickness behavior. Here, we confirm that TNF signaling hampers physical activity, food intake, and energy expenditure while enhancing glucose uptake by the liver and spleen, as well as controlling parasitemia in Plasmodium chabaudi (Pc)-infected mice. We also report that TNF is required for expression of inducible nitric oxide synthase (iNOS), stabilization of hypoxia-inducible factor 1α (HIF-1α), expression of glucose transporter GLUT1, and enhanced glycolysis in monocytic cells from Pc-infected mice. Importantly, Pc-infected Nos2-/-, TNFR1 cKO, and HIF-1a cKO mice show impaired release of TNF and glycolysis in monocytes, along with increased parasitemia and disease tolerance. Altogether, our results indicate that TNF-iNOS-HIF-1α-induced glycolysis in monocytes plays a critical role in host defense and sickness behavior in Pc-infected mice.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42506979 · DOI · PMC13405620
ATP13A4 gates extracellular polyamine levels to control excitatory synaptogenesis [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Polyamines, such as spermidine, are essential regulators of brain development, yet how cells control their uptake and extracellular levels remains unclear.
- Closing excerpt
- Thus, astrocytic polyamine clearance via ATP13A4 tunes extracellular spermidine to shape synapse formation during development.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (153 words)
Polyamines, such as spermidine, are essential regulators of brain development, yet how cells control their uptake and extracellular levels remains unclear. Here we show that ATP13A4, a transport protein enriched in glia and prominently expressed in astrocytes, governs brain polyamine balance. Using biochemical, cellular, and animal models, we find that ATP13A4 imports polyamines into cells and thereby limits their availability outside cells. Loss of ATP13A4 simplifies astrocyte morphology and increases the excitatory connections, or synapses, that astrocytes promote between neurons; adding spermidine reproduces these effects, identifying extracellular spermidine as a synapse-promoting signal. In mice lacking Atp13a4, brain polyamines are redistributed, with reduced levels in the cortex and accumulation in cerebrospinal fluid. This is accompanied by excess excitatory synapses, delayed early development, and mild, female-biased behavioral changes in adulthood. Rare ATP13A4 variants linked to neurodevelopmental disorders disrupt its function. Thus, astrocytic polyamine clearance via ATP13A4 tunes extracellular spermidine to shape synapse formation during development.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42680725 · DOI · PMC13534584
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Factors affecting spermatogenesis upon gonadotropin-replacement therapy: a meta-analytic study [4]
- Research article Multiethnic genome-wide meta-analysis of ectopic fat depots identifies loci associated with adipocyte development and differentiation [5]
- Research article Jak2 V617F clonal hematopoiesis promotes arterial thrombosis via platelet activation and cross talk [6]
- Research article Hippocampal neurogenesis and pattern separation: A meta-analysis of behavioral data [7]
- Research article Clonal hematopoiesis of indeterminate potential as a prognostic factor: a systematic review and meta-analysis [8]
- Research article Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis [9]
References
- Murano T, Hagihara H, Tajinda K, Takao K, Takamiya Y, Katoh K, et al.. Repetitive neuronal activation regulates cellular maturation state via nuclear reprogramming. . 2026. PMID 42469214 · DOI · PMC13379389
- Matteucci KC, Leite NPS, Assis PA, Hirako IC, Pioto F, Ojelabi O, et al.. Reprogramming of host energy metabolism mediated by the TNF-iNOS-HIF-1α axis plays a key role in host resistance to Plasmodium infection. . 2026. PMID 42506979 · DOI · PMC13405620
- van Veen S, Meeus E, Irala D, Sakers K, Liu Z, Savage J, et al.. ATP13A4 gates extracellular polyamine levels to control excitatory synaptogenesis. . 2026. PMID 42680725 · DOI · PMC13534584
- Rastrelli G, Corona G, Mannucci E, Maggi M. Factors affecting spermatogenesis upon gonadotropin-replacement therapy: a meta-analytic study. Andrology. 2014. PMID 25271205 · DOI
- Chu AY, Deng X, Fisher VA, Drong A, Zhang Y, Feitosa MF, et al.. Multiethnic genome-wide meta-analysis of ectopic fat depots identifies loci associated with adipocyte development and differentiation. Nat Genet. 2017. PMID 27918534 · DOI · PMC5451114
- Liu W, Pircher J, Schuermans A, Ul Ain Q, Zhang Z, Honigberg MC, et al.. Jak2 V617F clonal hematopoiesis promotes arterial thrombosis via platelet activation and cross talk. Blood. 2024. PMID 38142422 · DOI · PMC11033586
- França TFA, Bitencourt AM, Maximilla NR, Barros DM, Monserrat JM. Hippocampal neurogenesis and pattern separation: A meta-analysis of behavioral data. Hippocampus. 2017. PMID 28597491 · DOI
- Singh J, Li N, Ashrafi E, Thao LTP, Curtis DJ, Wood EM, et al.. Clonal hematopoiesis of indeterminate potential as a prognostic factor: a systematic review and meta-analysis. Blood Adv. 2024. PMID 38838228 · DOI · PMC11298876
- van Rooij FJA, Qayyum R, Smith AV, Zhou Y, Trompet S, Tanaka T, et al.. Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis. Am J Hum Genet. 2017. PMID 28017375 · DOI · PMC5223059
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
See how EvidenceLib is built. Spotted an error? Email support@evidencehelix.com.
Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.