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Record W7133075591

Understanding the Birth and Life of Mammalian Neural Stem Cells

2022· dissertation· W7133075591 on OpenAlexfundno aff
Danielle Jeong

Bibliographic record

VenueTSpace · 2022
Typedissertation
Language
FieldNeuroscience
TopicNeurogenesis and neuroplasticity mechanisms
Canadian institutionsnot available
FundersCanada First Research Excellence FundCanadian Institutes of Health ResearchHospital for Sick ChildrenUniversity of Toronto
KeywordsNeural stem cellEmbryonic stem cellStem cellNicheTranscriptomeAdult stem cellRegulatorNeurosphere
DOInot available

Abstract

fetched live from OpenAlex

Neural stem cells (NSCs) in the adult mammalian brain are found in germinal niches where they contribute to tissue homeostasis and neuroplasticity. One of these NSC niches is in the ventricular-subventricular zone (V-SVZ) along lateral ventricles. V-SVZ NSCs are defined by their ability to persist in a quiescent-like state and become activated to generate neurons for olfactory learning or oligodendrocytes for white matter repair. V-SVZ NSCs are also exposed to a plethora of signals in the niche environment that affect their function. How do these adult V-SVZ NSCs integrate information from the many signals in the environment to persist in a non-proliferating state, and become appropriately mobilized to attempt to repair the injured brain? This question is addressed by examining V-SVZ NSCs during two key events, preceding and following the time of mammalian birth, and during a demyelinating injury in the adult brain. The first part of the thesis asks how quiescent-like NSCs emerge from embryonic neural stem cells known as radial precursors (RPs) and describes a molecular mechanism that regulates this transition. LRIG1 was identified a negative regulator of the epidermal growth factor receptor in embryonic cortical RPs and that by inhibiting this pro-proliferative receptor, facilitates the transition of NSCs into the quiescent-like state. The second part of the thesis asks what determines the oligodendrogenic potential of adult V-SVZ NSCs during white matter repair. To address this, single-cell transcriptomic profiling was coupled with lineage tracing to follow the V-SVZ NSC response to a demyelinating injury. This analysis showed that quiescent-like V-SVZ NSCs become activated and undergo increased oligodendrogenesis without changing their transcriptional identity, suggesting that extrinsic cues in the injury environment activate NSCs to promote injury repair. Collectively, these findings highlight the importance of the environment in influencing the V-SVZ NSC fate and identify mechanisms that modulate the NSC response to niche cues.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0010.001
Scholarly communication0.0020.003
Open science0.0010.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0010.000

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 head0.115
GPT teacher head0.310
Teacher spread0.195 · 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 source (direct Gemma or distilled Codex), 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

Citations0
Published2022
Admission routes1
Has abstractyes

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