Evidence map›Paper›PMID 25700280›Full record

ArticleEMBO reports2015

Distinct germline progenitor subsets defined through Tsc2-mTORC1 signaling.

Robin M Hobbs, Hue M La, Juho-Antti Mäkelä, Toshiyuki Kobayashi, Tetsuo Noda, Pier Paolo Pandolfi

Open access · bronzeAbstract read
In one paragraph

Article in EMBO reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
3.5field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 66 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 5 institutions in 3 countries.

Robin M HobbsCancer Research Institute, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Beth Israel Deaconess Medical Center Harvard Medical School, Boston, MA, USA Australian Regenerative Medicine Institute and Department of Anatomy and Developmental Biology Monash University, Clayton, VIC, Australia ppandolf@bidmc.harvard.edu robin.hobbs@monash.edu.
Hue M LaAustralian Regenerative Medicine Institute and Department of Anatomy and Developmental Biology Monash University, Clayton, VIC, Australia.
Juho-Antti MäkeläAustralian Regenerative Medicine Institute and Department of Anatomy and Developmental Biology Monash University, Clayton, VIC, Australia.
Toshiyuki KobayashiDepartment of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, Japan.
Tetsuo NodaDepartment of Cell Biology, JFCR Cancer Institute, Tokyo, Japan.
Pier Paolo PandolfiCancer Research Institute, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Beth Israel Deaconess Medical Center Harvard Medical School, Boston, MA, USA ppandolf@bidmc.harvard.edu robin.hobbs@monash.edu.
Beth Israel Deaconess Medical Center · USAustralian Regenerative Medicine Institute · AUJuntendo University · JPMonash University · AUThe Cancer Institute Hospital · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Adult tissue maintenance is often dependent on resident stem cells; however, the phenotypic and functional heterogeneity existing within this self-renewing population is poorly understood. Here, we define distinct subsets of undifferentiated spermatogonia (spermatogonial progenitor cells; SPCs) by differential response to hyperactivation of mTORC1, a key growth-promoting pathway. We find that conditional deletion of the mTORC1 inhibitor Tsc2 throughout the SPC pool using Vasa-Cre promotes differentiation at the expense of self-renewal and leads to germline degeneration. Surprisingly, Tsc2 ablation within a subset of SPCs using Stra8-Cre did not compromise SPC function. SPC activity also appeared unaffected by Amh-Cre-mediated Tsc2 deletion within somatic cells of the niche. Importantly, we find that differentiation-prone SPCs have elevated mTORC1 activity when compared to SPCs with high self-renewal potential. Moreover, SPCs insensitive to Tsc2 deletion are preferentially associated with mTORC1-active committed progenitor fractions. We therefore delineate SPC subsets based on differential mTORC1 activity and correlated sensitivity to Tsc2 deletion. We propose that mTORC1 is a key regulator of SPC fate and defines phenotypically distinct SPC subpopulations with varying propensities for self-renewal and differentiation.

Indexed as

Adaptor Proteins, Signal TransducingAdult Stem CellsAnimalsCell DifferentiationCell LineageCell ProliferationDEAD-box RNA HelicasesFemaleGene DeletionGene Expression RegulationGenetic EngineeringIntegrasesMaleMechanistic Target of Rapamycin Complex 1MiceMice, TransgenicAdaptor Proteins, Signal TransducingCre recombinaseDdx4 protein, mouseDEAD-box RNA HelicasesIntegrasesMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesStra8 protein, mouseTOR Serine-Threonine KinasesTsc2 protein, mouseTuberous Sclerosis Complex 2 ProteinTumor Suppressor Proteinsdifferentiationgermline stem cellsmTORC1

Identifiers

PMID25700280
PMCPMC4388613
OpenAlexW2006321057

What OpenQuestion holds

Textmetadata
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.