MicroRNA-103/107 family regulates multiple epithelial stem cell characteristics

Han Peng; Jong Kook Park; Julia Katsnelson; Nihal Kaplan; Wending Yang; Spiro Getsios; Robert M. Lavker

doi:10.1002/stem.1962

MicroRNA-103/107 family regulates multiple epithelial stem cell characteristics

Han Peng, Jong Kook Park, Julia Katsnelson, Nihal Kaplan, Wending Yang, Spiro Getsios, Robert M. Lavker^*

^*Corresponding author for this work

Dermatology

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

Abstract

The stem cell niche is thought to affect cell cycle quiescence, proliferative capacity, and communication between stem cells and their neighbors. How these activities are controlled is not completely understood. Here we define a microRNA family (miRs-103/107) preferentially expressed in the stem cell-enriched limbal epithelium that regulates and integrates these stem cell characteristics. miRs-103/107 target the ribosomal kinase p90RSK2, thereby arresting cells in G0/G1 and contributing to a slow-cycling phenotype. Furthermore, miRs-103/107 increase the proliferative capacity of keratinocytes by targeting Wnt3a, which enhances Sox9 and YAP1 levels and thus promotes a stem cell phenotype. This miRNA family also regulates keratinocyte cell-cell communication by targeting: (a) the scaffolding protein NEDD9, preserving E-cadherin-mediated cell adhesion; and (b) the tyrosine phosphatase PTPRM, which negatively regulates connexin 43-based gap junctions. We propose that such regulation of cell communication and adhesion molecules maintains the integrity of the stem cell niche ultimately preserving self-renewal, a hallmark of epithelial stem cells.

Original language	English (US)
Pages (from-to)	1642-1656
Number of pages	15
Journal	Stem Cells
Volume	33
Issue number	5
DOIs	https://doi.org/10.1002/stem.1962
State	Published - May 1 2015

Keywords

Adherens junctions
Cell cycle
Cell-cell communication
Gap junctions
Proliferative capacity
Wnt signaling

ASJC Scopus subject areas

Medicine(all)

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10.1002/stem.1962

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title = "MicroRNA-103/107 family regulates multiple epithelial stem cell characteristics",

abstract = "The stem cell niche is thought to affect cell cycle quiescence, proliferative capacity, and communication between stem cells and their neighbors. How these activities are controlled is not completely understood. Here we define a microRNA family (miRs-103/107) preferentially expressed in the stem cell-enriched limbal epithelium that regulates and integrates these stem cell characteristics. miRs-103/107 target the ribosomal kinase p90RSK2, thereby arresting cells in G0/G1 and contributing to a slow-cycling phenotype. Furthermore, miRs-103/107 increase the proliferative capacity of keratinocytes by targeting Wnt3a, which enhances Sox9 and YAP1 levels and thus promotes a stem cell phenotype. This miRNA family also regulates keratinocyte cell-cell communication by targeting: (a) the scaffolding protein NEDD9, preserving E-cadherin-mediated cell adhesion; and (b) the tyrosine phosphatase PTPRM, which negatively regulates connexin 43-based gap junctions. We propose that such regulation of cell communication and adhesion molecules maintains the integrity of the stem cell niche ultimately preserving self-renewal, a hallmark of epithelial stem cells.",

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author = "Han Peng and Park, {Jong Kook} and Julia Katsnelson and Nihal Kaplan and Wending Yang and Spiro Getsios and Lavker, {Robert M.}",

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year = "2015",

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doi = "10.1002/stem.1962",

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AU - Peng, Han

AU - Park, Jong Kook

AU - Katsnelson, Julia

AU - Kaplan, Nihal

AU - Yang, Wending

AU - Getsios, Spiro

AU - Lavker, Robert M.

PY - 2015/5/1

Y1 - 2015/5/1

N2 - The stem cell niche is thought to affect cell cycle quiescence, proliferative capacity, and communication between stem cells and their neighbors. How these activities are controlled is not completely understood. Here we define a microRNA family (miRs-103/107) preferentially expressed in the stem cell-enriched limbal epithelium that regulates and integrates these stem cell characteristics. miRs-103/107 target the ribosomal kinase p90RSK2, thereby arresting cells in G0/G1 and contributing to a slow-cycling phenotype. Furthermore, miRs-103/107 increase the proliferative capacity of keratinocytes by targeting Wnt3a, which enhances Sox9 and YAP1 levels and thus promotes a stem cell phenotype. This miRNA family also regulates keratinocyte cell-cell communication by targeting: (a) the scaffolding protein NEDD9, preserving E-cadherin-mediated cell adhesion; and (b) the tyrosine phosphatase PTPRM, which negatively regulates connexin 43-based gap junctions. We propose that such regulation of cell communication and adhesion molecules maintains the integrity of the stem cell niche ultimately preserving self-renewal, a hallmark of epithelial stem cells.

AB - The stem cell niche is thought to affect cell cycle quiescence, proliferative capacity, and communication between stem cells and their neighbors. How these activities are controlled is not completely understood. Here we define a microRNA family (miRs-103/107) preferentially expressed in the stem cell-enriched limbal epithelium that regulates and integrates these stem cell characteristics. miRs-103/107 target the ribosomal kinase p90RSK2, thereby arresting cells in G0/G1 and contributing to a slow-cycling phenotype. Furthermore, miRs-103/107 increase the proliferative capacity of keratinocytes by targeting Wnt3a, which enhances Sox9 and YAP1 levels and thus promotes a stem cell phenotype. This miRNA family also regulates keratinocyte cell-cell communication by targeting: (a) the scaffolding protein NEDD9, preserving E-cadherin-mediated cell adhesion; and (b) the tyrosine phosphatase PTPRM, which negatively regulates connexin 43-based gap junctions. We propose that such regulation of cell communication and adhesion molecules maintains the integrity of the stem cell niche ultimately preserving self-renewal, a hallmark of epithelial stem cells.

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MicroRNA-103/107 family regulates multiple epithelial stem cell characteristics

Abstract

Keywords

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