TGF-β Family Signaling in Embryonic and Somatic Stem-Cell Renewal and Differentiation
Bibliographic record
Abstract
Soon after the discovery of transforming growth factor-b (TGF-b), seminal work in vertebrate and invertebrate models revealed the TGF-b family to be central regulators of tissue morphogenesis.Members of the TGF-b family direct some of the earliest cell-fate decisions in animal development, coordinate complex organogenesis, and contribute to tissue homeostasis in the adult.Here, we focus on the role of the TGF-b family in mammalian stem-cell biology and discuss its wide and varied activities both in the regulation of pluripotency and in cell-fate commitment.S tem cells are defined by their ability to divide continually to maintain the stem-cell pool and to provide progeny that differentiate into other cell types.These defining qualities are established by internal transcriptional programs that interact with the local environment, or niche, to both promote stem-cell maintenance and drive cell-fate determination (Voog and Jones 2010;Young 2011;Scadden 2014;Kfoury and Scadden 2015).Members of the TGF-b family of signaling ligands are key components of the stem-cell niche for both embryonic and somatic stem cells and orchestrate diverse responses in different types of stem cells.Here, we provide an overview of the general characteristics of embryonic versus somatic stem cells, briefly introduce key concepts in understanding the core TGF-b family Smad signaling pathway, and then delve into the function of TGF-b family signaling in various embryonic and somatic stem-cell systems. EMBRYONIC AND SOMATIC STEM CELLSAfter fertilization, the zygote divides to form the morula and then the blastocyst.The blastocyst consists of an outer layer of cells, called the trophoblast, an inner cavity of fluid, called the blastocele, and an internal cluster of cells, called the inner cell mass (ICM) (Rossant 2008).The embryo forms from the cells of the ICM, and these cells can be isolated and cultured ex vivo to give rise to embryonic stem cells (ESCs) (Fig. 1A).Naı ¨ve epiblast cells from within the ICM
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.004 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".