Dataset Information

Tracing the cellular dynamics of sebaceous gland development in normal and perturbed states.

ABSTRACT: The sebaceous gland (SG) is an essential component of the skin, and SG dysfunction is debilitating^1,2. Yet, the cellular bases for its origin, development and subsequent maintenance remain poorly understood. Here, we apply large-scale quantitative fate mapping to define the patterns of cell fate behaviour during SG development and maintenance. We show that the SG develops from a defined number of lineage-restricted progenitors that undergo a programme of independent and stochastic cell fate decisions. Following an expansion phase, equipotent progenitors transition into a phase of homeostatic turnover, which is correlated with changes in the mechanical properties of the stroma and spatial restrictions on gland size. Expression of the oncogene KrasG12D results in a release from these constraints and unbridled gland expansion. Quantitative clonal fate analysis reveals that, during this phase, the primary effect of the Kras oncogene is to drive a constant fate bias with little effect on cell division rates. These findings provide insight into the developmental programme of the SG, as well as the mechanisms that drive tumour progression and gland dysfunction.

SUBMITTER: Andersen MS

PROVIDER: S-EPMC6978139 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Tracing the cellular dynamics of sebaceous gland development in normal and perturbed states.

Andersen Marianne Stemann MS Hannezo Edouard E Ulyanchenko Svetlana S Estrach Soline S Antoku Yasuko Y Pisano Sabrina S Boonekamp Kim E KE Sendrup Sarah S Maimets Martti M Pedersen Marianne Terndrup MT Johansen Jens V JV Clement Ditte L DL Feral Chloe C CC Simons Benjamin D BD Jensen Kim B KB

Nature cell biology 20190729 8

The sebaceous gland (SG) is an essential component of the skin, and SG dysfunction is debilitating<sup>1,2</sup>. Yet, the cellular bases for its origin, development and subsequent maintenance remain poorly understood. Here, we apply large-scale quantitative fate mapping to define the patterns of cell fate behaviour during SG development and maintenance. We show that the SG develops from a defined number of lineage-restricted progenitors that undergo a programme of independent and stochastic cel ...[more]

PMID: 31358966

Similar Datasets

Project description:PurposeEyelid sebaceous gland carcinoma (SGC) is a malignancy with fatal risk, high recurrence rate, and pagetoid spread. Thus, recurrence risk prediction and prompt treatment are extremely important. This study aimed to develop a nomogram to predict SGC recurrence based on potential risk factors.MethodsWe conducted a retrospective study to train and test a nomogram based on the clinical data of 391 patients across our hospital (304) and other grass-roots hospitals (87). After Cox regression, predictors included in the nomogram were selected, and sensitivity, specificity, concordance index (C-index), etc., were calculated to test their discrimination ability.ResultsAfter a median follow-up period of 4.12 years, SGC recurred in 52 (17.11%) patients. The 1-, 2-, and 5-year recurrence-free survival rates were 88.3%, 85.4%, and 81.6%, respectively. We examined five risk factors, such as lymph node metastasis at initial diagnosis (hazard ratio [HR], 2.260; 95% confidence interval [CI], 1.021-5.007), Ki67 (HR, 1.036; 95% CI, 1.020-1.052), histology differentiation degree (HR, 2.274; 95% CI, 1.063-4.865), conjunctival pagetoid infiltration (HR, 2.100; 95% CI, 1.0058-4.167), and orbital involvement (HR, 4.764; 95% CI, 1.436-15.803). The model had good discrimination in both internal and external test sets. The model had good discrimination in both internal and external test sets. The sensitivity of the internal test and external test set were 0.722 and 0.806, respectively, and specificity of the internal test and external test set were 0.886 and 0.893, respectively.ConclusionWe examined the potential risk factors for eyelid SGC recurrence and constructed a nomogram, which complements the TNM system in terms of prediction, indicating that our nomogram has the potential to reach clinical significance. This nomogram has the potential to assist healthcare practitioners in promptly detecting patients who are at an elevated risk and in tailoring clinical interventions to meet their individualized needs.

Dataset Information

Tracing the cellular dynamics of sebaceous gland development in normal and perturbed states.

Publications

Tracing the cellular dynamics of sebaceous gland development in normal and perturbed states.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets