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Record W3096497980 · doi:10.1002/advs.202002261

Loss of <i>β</i> ‐Actin Leads to Accelerated Mineralization and Dysregulation of Osteoblast‐Differentiation Genes during Osteogenic Reprogramming

2020· article· en· W3096497980 on OpenAlexfundno aff
Tamara Gjorgjieva, Xin Xie, Patrick Commins, Syed Raza Mahmood, Kristin C. Gunsalus, Pancě Naumov, Piergiorgio Percipalle

Bibliographic record

VenueAdvanced Science · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBone Metabolism and Diseases
Canadian institutionsnot available
FundersCancerfondenYork UniversityVetenskapsrådetNew York University Abu DhabiSheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences
KeywordsReprogrammingOsteoblastCell biologyMineralization (soil science)GeneChemistryMaterials scienceBiologyBiochemistryIn vitro

Abstract

fetched live from OpenAlex

Abstract Actin plays fundamental roles in both the cytoplasm and the cell nucleus. In the nucleus, β ‐actin regulates neuronal reprogramming by consolidating a heterochromatin landscape required for transcription of neuronal gene programs, yet it remains unknown whether it has a role in other differentiation models. To explore the potential roles of β ‐actin in osteogenesis, β ‐actin wild‐type (WT) and β ‐actin knockout (KO) mouse embryonic fibroblasts (MEFs) are reprogrammed to osteoblast‐like cells using small molecules in vitro. It is discovered that loss of β ‐actin leads to an accelerated mineralization phenotype (hypermineralization), accompanied with enhanced formation of extracellular hydroxyapatite microcrystals, which originate in the mitochondria in the form of microgranules. This phenotype is a consequence of rapid upregulation of mitochondrial genes including those involved in oxidative phosphorylation (OXPHOS) in reprogrammed KO cells. It is further found that osteogenic gene programs are differentially regulated between WT and KO cells, with clusters of genes exhibiting different temporal expression patterns. A novel function for β ‐actin in osteogenic reprogramming through a mitochondria‐based mechanism that controls cell‐mediated mineralization is proposed.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.055
Threshold uncertainty score0.278

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.012
GPT teacher head0.256
Teacher spread0.244 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations22
Published2020
Admission routes1
Has abstractyes

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