PYY regulates human skeletal muscle progenitor cell proliferation
Notice bibliographique
Résumé
Adult skeletal muscle stem cells (satellite cells) are required for regeneration after injury. The regulation of regeneration has not been fully elucidated, but relies on factors both intrinsic and extrinsic to the satellite cells. Identifying and characterizing factors that influence satellite cell proliferation is necessary for the development of therapies to aid with muscle‐related disorders. We have recently shown that peptide YY (PYY) is temporally expressed and likely synthesized in differentiating muscle progenitor cells (MPCs). The function(s) of intrinsic or extrinsic PYY in MPCs is currently unknown. PYY is a ligand for the Y receptors. Activation of the Y receptors has been shown to allow stem cells to remain in a proliferative state even in the absence of fibroblast growth factor (FGF), a critical proliferative regulator. Objective Our objectives were 1) to determine the PYY protein levels over time in proliferating MPCs, and 2) to evaluate the effect of exogenous PYY on human MPC proliferation in the presence and absence of FGF. Methods Human MPCs were obtained from 4 young female donors via vastus lateralis muscle biopsies. MPCs were sorted to produce a homogenous culture. MPCs were maintained in the proliferative state in a growth media (GM) containing Ham's F12, 20% fetal bovine serum, and 5 ng/mL bFGF. Study 1: MPCs were grown in GM. PYY protein levels were measured by an In‐Cell Western ™ assay on days 5, 6, and 7 of proliferation. Study 2: Three days after seeding MPCs in GM, cultures were switched to one of four media: 1) GM with 5 ng/mL bFGF (CON); 2) GM without bFGF (noFGF); 3) GM with a physiologically relevant dose of PYY (500 pM) but without bFGF (Norm‐PYY); 4) GM with a supra‐physiological dose of PYY (1 nM) but without bFGF (High‐PYY) and grown for an additional 4 days. Using the Celigo® Cell Imaging Cytometer, percent confluence was tracked daily. On days 5, 6, and 7, MPCs were stained to identify the number of nuclei and the number of dead cells. Results PYY protein levels were detectible in MPCs at days 5, 6, and 7 of proliferation. PYY levels were lower on day 7 compared to days 5 (p<0.001) and 6 (p<0.001). Percent confluence area under the curve (days 2–7) was greater in Norm‐PYY compared to both CON (p<0.01) and noFGF (p<0.05) but not High‐PYY. After 7 days of proliferation noFGF cells had fewer nuclei than CON (p<0.05) showing that removal of bFGF reduced proliferative ability of MPCs. In Norm‐PYY, nuclei count was greater (day 7) than noFGF (p<0.001) but not different from CON suggesting that PYY rescued the proliferative ability that was lost when FGF was removed from the media. Conclusion MPCs likely synthesize PYY throughout proliferation in a temporal fashion that may be related to the proliferative capacity of the cell. PYY exerts a pro‐proliferative effect on MPCs in culture, possibly, through a mechanism similar to FGF. Support or Funding Information Cornell University, Canadian Institute for Health Research Doctoral Foreign Study Award
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».