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

Marianne Stemann Andersen; Edouard Hannezo; Svetlana Ulyanchenko; Soline Estrach; Yasuko Antoku; Sabrina Pisano; Kim E. Boonekamp; Sarah Sendrup; Martti Maimets; Marianne Terndrup Pedersen; Jens V. Johansen; Ditte L. Clement; Chloe C. Feral; Benjamin D. Simons; Kim B. Jensen

doi:10.1038/s41556-019-0362-x

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

Marianne Stemann Andersen, Edouard Hannezo, Svetlana Ulyanchenko, Soline Estrach, Yasuko Antoku, Sabrina Pisano, Kim E. Boonekamp, Sarah Sendrup, Martti Maimets, Marianne Terndrup Pedersen, Jens V. Johansen, Ditte L. Clement, Chloe C. Feral, Benjamin D. Simons, Kim B. Jensen^*

^*Corresponding author for this work

10 Citations (Scopus)

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.

Original language	English
Journal	Nature Cell Biology
Volume	21
Issue number	8
Pages (from-to)	924-932
Number of pages	9
ISSN	1465-7392
DOIs	https://doi.org/10.1038/s41556-019-0362-x
Publication status	Published - 2019

Access to Document

10.1038/s41556-019-0362-x

Cite this

Andersen, M. S., Hannezo, E., Ulyanchenko, S., Estrach, S., Antoku, Y., Pisano, S., Boonekamp, K. E., Sendrup, S., Maimets, M., Pedersen, M. T., Johansen, J. V., Clement, D. L., Feral, C. C., Simons, B. D., & Jensen, K. B. (2019). Tracing the cellular dynamics of sebaceous gland development in normal and perturbed states. Nature Cell Biology, 21(8), 924-932. https://doi.org/10.1038/s41556-019-0362-x

Andersen, MS, Hannezo, E, Ulyanchenko, S, Estrach, S, Antoku, Y, Pisano, S, Boonekamp, KE, Sendrup, S, Maimets, M , Pedersen, MT , Johansen, JV, Clement, DL, Feral, CC, Simons, BD & Jensen, KB 2019, 'Tracing the cellular dynamics of sebaceous gland development in normal and perturbed states', Nature Cell Biology, vol. 21, no. 8, pp. 924-932. https://doi.org/10.1038/s41556-019-0362-x

@article{89b6251c3dd240c890f7ac8e2ebf827d,

title = "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 debilitating1,2. 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.",

author = "Andersen, {Marianne Stemann} and Edouard Hannezo and Svetlana Ulyanchenko and Soline Estrach and Yasuko Antoku and Sabrina Pisano and Boonekamp, {Kim E.} and Sarah Sendrup and Martti Maimets and Pedersen, {Marianne Terndrup} and Johansen, {Jens V.} and Clement, {Ditte L.} and Feral, {Chloe C.} and Simons, {Benjamin D.} and Jensen, {Kim B.}",

year = "2019",

doi = "10.1038/s41556-019-0362-x",

language = "English",

volume = "21",

pages = "924--932",

journal = "Nature Cell Biology",

issn = "1465-7392",

publisher = "nature publishing group",

number = "8",

}

TY - JOUR

T1 - Tracing the cellular dynamics of sebaceous gland development in normal and perturbed states

AU - Andersen, Marianne Stemann

AU - Hannezo, Edouard

AU - Ulyanchenko, Svetlana

AU - Estrach, Soline

AU - Antoku, Yasuko

AU - Pisano, Sabrina

AU - Boonekamp, Kim E.

AU - Sendrup, Sarah

AU - Maimets, Martti

AU - Pedersen, Marianne Terndrup

AU - Johansen, Jens V.

AU - Clement, Ditte L.

AU - Feral, Chloe C.

AU - Simons, Benjamin D.

AU - Jensen, Kim B.

PY - 2019

Y1 - 2019

N2 - The sebaceous gland (SG) is an essential component of the skin, and SG dysfunction is debilitating1,2. 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.

AB - The sebaceous gland (SG) is an essential component of the skin, and SG dysfunction is debilitating1,2. 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.

U2 - 10.1038/s41556-019-0362-x

DO - 10.1038/s41556-019-0362-x

M3 - Journal article

C2 - 31358966

AN - SCOPUS:85069945675

SN - 1465-7392

VL - 21

SP - 924

EP - 932

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 8

ER -

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

Abstract

Access to Document

Fingerprint

Cite this