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http://hdl.handle.net/1942/35883
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DC Field | Value | Language |
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dc.contributor.author | Vennekens, A | - |
dc.contributor.author | Laporte , E | - |
dc.contributor.author | HERMANS, Florian | - |
dc.contributor.author | Cox , B | - |
dc.contributor.author | Modave, E | - |
dc.contributor.author | Janiszewski, A | - |
dc.contributor.author | Nys, C | - |
dc.contributor.author | Kobayashi, H | - |
dc.contributor.author | Malengier-Devlies, B | - |
dc.contributor.author | Chappell, J | - |
dc.contributor.author | Matthys , P | - |
dc.contributor.author | Garcia, MI | - |
dc.contributor.author | Pasque, V | - |
dc.contributor.author | Lambrechts, D | - |
dc.contributor.author | Vankelecom, H | - |
dc.date.accessioned | 2021-11-25T10:37:25Z | - |
dc.date.available | 2021-11-25T10:37:25Z | - |
dc.date.issued | 2021 | - |
dc.date.submitted | 2021-09-13T15:14:07Z | - |
dc.identifier.citation | Proceedings of the National Academy of Sciences of the United States of America, 118 (25) (Art N° e2100052118) | - |
dc.identifier.uri | http://hdl.handle.net/1942/35883 | - |
dc.description.abstract | Stem cells in the adult pituitary are quiescent yet show acute activation upon tissue injury. The molecular mechanisms underlying this reaction are completely unknown. We applied single-cell transcriptomics to start unraveling the acute pituitary stem cell activation process as occurring upon targeted endocrine cell-ablation damage. This stem cell reaction was contrasted with the aging (middle-aged) pituitary, known to have lost damage-repair capacity. Stem cells in the aging pituitary show regressed proliferative activation upon injury and diminished in vitro organoid formation. Single-cell RNA sequencing uncovered interleukin-6 (IL-6) as being up-regulated upon damage, however only in young but not aging pituitary. Administering IL-6 to young mice promptly triggered pituitary stem cell proliferation, while blocking IL-6 or associated signaling pathways inhibited such reaction to damage. By contrast, IL-6 did not generate a pituitary stem cell activation response in aging mice, coinciding with elevated basal IL-6 levels and raised inflammatory state in the aging gland (inflammaging). Intriguingly, in vitro stem cell activation by IL-6 was discerned in organoid culture not only from young but also from aging pituitary, indicating that the aging gland's stem cells retain intrinsic activatability in vivo, likely impeded by the prevailing inflammatory tissue milieu. Importantly, IL-6 supplementation strongly enhanced the growth capability of pituitary stem cell organoids, thereby expanding their potential as an experimental model. Our study identifies IL-6 as a pituitary stem cell activator upon local damage, a competence quenched at aging, concomitant with raised IL-6/inflammatory levels in the older gland. These insights may open the way to interfering with pituitary aging. | - |
dc.description.sponsorship | We thank Y. Van Goethem and V. Vanslembrouck for valuable technical help. We thank the Vlaams Instituut voor Biotechnologie (VIB) Nucleomics Core (in particular Rekin’s Janky) and Katholieke Universiteit (KU) Leuven Genomics Core (particularly Álvaro Cortés Calabuig) for their expert assistance in scRNA-seq analysis, as well as Thomas Van Brussel and Bram Boeckx (D.L.’s group, KU Leuven) for technical and bioinformatical support in scRNA-seq experiments, respectively. The computational resources used for scRNA-seq analysis were provided by the Vlaams Supercomputer Centrum,managed by the Fonds Wetenschappelijk Onderzoek (FWO)–Vlaanderen. We are also grateful to the Imaging Core (VIB, KU Leuven) and the Cell and Tissue Imaging Cluster (KU Leuven) for the use of microscopes and the Center for Brain and Disease Research Histology unit (VIB, KU Leuven) for the use of histology equipment. We acknowledge the use of the Electron Microscopy Platform (VIB, KU Leuven) and the Institute of Development, Aging and Cancer (Tohoku University, Sendai, Japan) for transmission electron microscopy. This work was supported by several grants from the Bijzonder Onderzoeksfonds KU Leuven and from Fonds voor Wetenschappelijk Onderzoek (FWO)–Vlaanderen awarded to the principal investigators. A.V. (Grant No. 1141717N), E.L. (Grant No. 11A3320N), B.C. (Grant No. 11W9215N), A.J. (Grant No. 1158318N), and C.N. (Grant No. 1S14218N) are supported by a PhD Fellowship from the FWO/FWOStrategisch Basisonderzoek (SB). | - |
dc.language.iso | en | - |
dc.publisher | NATL ACAD SCIENCES | - |
dc.subject.other | pituitary | - |
dc.subject.other | stem cells | - |
dc.subject.other | interleukin-6 | - |
dc.subject.other | aging | - |
dc.subject.other | organoids | - |
dc.title | Interleukin-6 is an activator of pituitary stem cells upon local damage, a competence quenched in the aging gland | - |
dc.type | Journal Contribution | - |
dc.identifier.issue | 25 | - |
dc.identifier.volume | 118 | - |
local.bibliographicCitation.jcat | A1 | - |
local.publisher.place | 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
local.bibliographicCitation.artnr | e2100052118 | - |
dc.identifier.doi | 10.1073/pnas.2100052118 | - |
dc.identifier.pmid | 34161279 | - |
dc.identifier.isi | 000672806300002 | - |
dc.identifier.eissn | - | |
local.provider.type | Web of Science | - |
local.uhasselt.international | yes | - |
item.fullcitation | Vennekens, A; Laporte , E; HERMANS, Florian; Cox , B; Modave, E; Janiszewski, A; Nys, C; Kobayashi, H; Malengier-Devlies, B; Chappell, J; Matthys , P; Garcia, MI; Pasque, V; Lambrechts, D & Vankelecom, H (2021) Interleukin-6 is an activator of pituitary stem cells upon local damage, a competence quenched in the aging gland. In: Proceedings of the National Academy of Sciences of the United States of America, 118 (25) (Art N° e2100052118). | - |
item.accessRights | Open Access | - |
item.fulltext | With Fulltext | - |
item.validation | ecoom 2022 | - |
item.contributor | Vennekens, A | - |
item.contributor | Laporte , E | - |
item.contributor | HERMANS, Florian | - |
item.contributor | Cox , B | - |
item.contributor | Modave, E | - |
item.contributor | Janiszewski, A | - |
item.contributor | Nys, C | - |
item.contributor | Kobayashi, H | - |
item.contributor | Malengier-Devlies, B | - |
item.contributor | Chappell, J | - |
item.contributor | Matthys , P | - |
item.contributor | Garcia, MI | - |
item.contributor | Pasque, V | - |
item.contributor | Lambrechts, D | - |
item.contributor | Vankelecom, H | - |
crisitem.journal.issn | 0027-8424 | - |
crisitem.journal.eissn | 1091-6490 | - |
Appears in Collections: | Research publications |
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File | Description | Size | Format | |
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Interleukin-6 is an activator of pituitary stem cells upon local damage, a competence quenched in the aging gland.pdf Restricted Access | Published version | 1.97 MB | Adobe PDF | View/Open Request a copy |
523581_2_merged_1621272227.pdf | Peer-reviewed author version | 7.39 MB | Adobe PDF | View/Open |
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