Human embryonic stem cells in culture possess primary cilia with hedgehog signaling machinery.

Enko N Kiprilov; Aashir Awan; Romain Desprat; Michelle Velho; Christian A Clement; Anne Grete Byskov; Claus Y Andersen; Peter Satir; Eric E Bouhassira; Søren T Christensen; Rhoda Elison Hirsch

doi:10.1083/jcb.200706028

Human embryonic stem cells in culture possess primary cilia with hedgehog signaling machinery.

Enko N Kiprilov, Aashir Awan, Romain Desprat, Michelle Velho, Christian A Clement, Anne Grete Byskov, Claus Y Andersen, Peter Satir, Eric E Bouhassira, Søren T Christensen, Rhoda Elison Hirsch

Cellebiologi og Fysiologi

105 Citationer (Scopus)

Abstract

Human embryonic stem cells (hESCs) are potential therapeutic tools and models of human development. With a growing interest in primary cilia in signal transduction pathways that are crucial for embryological development and tissue differentiation and interest in mechanisms regulating human hESC differentiation, demonstrating the existence of primary cilia and the localization of signaling components in undifferentiated hESCs establishes a mechanistic basis for the regulation of hESC differentiation. Using electron microscopy (EM), immunofluorescence, and confocal microscopies, we show that primary cilia are present in three undifferentiated hESC lines. EM reveals the characteristic 9 + 0 axoneme. The number and length of cilia increase after serum starvation. Important components of the hedgehog (Hh) pathway, including smoothened, patched 1 (Ptc1), and Gli1 and 2, are present in the cilia. Stimulation of the pathway results in the concerted movement of Ptc1 out of, and smoothened into, the primary cilium as well as up-regulation of GLI1 and PTC1. These findings show that hESCs contain primary cilia associated with working Hh machinery.
Udgivelsesdato: 2008-Mar-10

Originalsprog	Engelsk
Tidsskrift	Journal of Cell Biology
Vol/bind	180
Udgave nummer	5
Sider (fra-til)	897-904
Antal sider	7
ISSN	0021-9525
DOI	https://doi.org/10.1083/jcb.200706028
Status	Udgivet - 2008

Adgang til dokumentet

10.1083/jcb.200706028

Citationsformater

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title = "Human embryonic stem cells in culture possess primary cilia with hedgehog signaling machinery.",

abstract = "Human embryonic stem cells (hESCs) are potential therapeutic tools and models of human development. With a growing interest in primary cilia in signal transduction pathways that are crucial for embryological development and tissue differentiation and interest in mechanisms regulating human hESC differentiation, demonstrating the existence of primary cilia and the localization of signaling components in undifferentiated hESCs establishes a mechanistic basis for the regulation of hESC differentiation. Using electron microscopy (EM), immunofluorescence, and confocal microscopies, we show that primary cilia are present in three undifferentiated hESC lines. EM reveals the characteristic 9 + 0 axoneme. The number and length of cilia increase after serum starvation. Important components of the hedgehog (Hh) pathway, including smoothened, patched 1 (Ptc1), and Gli1 and 2, are present in the cilia. Stimulation of the pathway results in the concerted movement of Ptc1 out of, and smoothened into, the primary cilium as well as up-regulation of GLI1 and PTC1. These findings show that hESCs contain primary cilia associated with working Hh machinery. Udgivelsesdato: 2008-Mar-10",

author = "Kiprilov, {Enko N} and Aashir Awan and Romain Desprat and Michelle Velho and Clement, {Christian A} and Byskov, {Anne Grete} and Andersen, {Claus Y} and Peter Satir and Bouhassira, {Eric E} and Christensen, {S{\o}ren T} and Hirsch, {Rhoda Elison}",

note = "Keywords: Axoneme; Cell Differentiation; Cell Line; Cell Lineage; Cilia; Culture Media, Serum-Free; Embryonic Stem Cells; Female; Fluorescent Antibody Technique; Hedgehog Proteins; Humans; Kruppel-Like Transcription Factors; Male; Microscopy, Confocal; Microscopy, Electron, Transmission; Nuclear Proteins; Receptors, Cell Surface; Signal Transduction; Transcription Factors",

year = "2008",

doi = "10.1083/jcb.200706028",

language = "English",

volume = "180",

pages = "897--904",

journal = "Journal of Cell Biology",

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T1 - Human embryonic stem cells in culture possess primary cilia with hedgehog signaling machinery.

AU - Kiprilov, Enko N

AU - Awan, Aashir

AU - Desprat, Romain

AU - Velho, Michelle

AU - Clement, Christian A

AU - Byskov, Anne Grete

AU - Andersen, Claus Y

AU - Satir, Peter

AU - Bouhassira, Eric E

AU - Christensen, Søren T

AU - Hirsch, Rhoda Elison

N1 - Keywords: Axoneme; Cell Differentiation; Cell Line; Cell Lineage; Cilia; Culture Media, Serum-Free; Embryonic Stem Cells; Female; Fluorescent Antibody Technique; Hedgehog Proteins; Humans; Kruppel-Like Transcription Factors; Male; Microscopy, Confocal; Microscopy, Electron, Transmission; Nuclear Proteins; Receptors, Cell Surface; Signal Transduction; Transcription Factors

PY - 2008

Y1 - 2008

N2 - Human embryonic stem cells (hESCs) are potential therapeutic tools and models of human development. With a growing interest in primary cilia in signal transduction pathways that are crucial for embryological development and tissue differentiation and interest in mechanisms regulating human hESC differentiation, demonstrating the existence of primary cilia and the localization of signaling components in undifferentiated hESCs establishes a mechanistic basis for the regulation of hESC differentiation. Using electron microscopy (EM), immunofluorescence, and confocal microscopies, we show that primary cilia are present in three undifferentiated hESC lines. EM reveals the characteristic 9 + 0 axoneme. The number and length of cilia increase after serum starvation. Important components of the hedgehog (Hh) pathway, including smoothened, patched 1 (Ptc1), and Gli1 and 2, are present in the cilia. Stimulation of the pathway results in the concerted movement of Ptc1 out of, and smoothened into, the primary cilium as well as up-regulation of GLI1 and PTC1. These findings show that hESCs contain primary cilia associated with working Hh machinery. Udgivelsesdato: 2008-Mar-10

AB - Human embryonic stem cells (hESCs) are potential therapeutic tools and models of human development. With a growing interest in primary cilia in signal transduction pathways that are crucial for embryological development and tissue differentiation and interest in mechanisms regulating human hESC differentiation, demonstrating the existence of primary cilia and the localization of signaling components in undifferentiated hESCs establishes a mechanistic basis for the regulation of hESC differentiation. Using electron microscopy (EM), immunofluorescence, and confocal microscopies, we show that primary cilia are present in three undifferentiated hESC lines. EM reveals the characteristic 9 + 0 axoneme. The number and length of cilia increase after serum starvation. Important components of the hedgehog (Hh) pathway, including smoothened, patched 1 (Ptc1), and Gli1 and 2, are present in the cilia. Stimulation of the pathway results in the concerted movement of Ptc1 out of, and smoothened into, the primary cilium as well as up-regulation of GLI1 and PTC1. These findings show that hESCs contain primary cilia associated with working Hh machinery. Udgivelsesdato: 2008-Mar-10

U2 - 10.1083/jcb.200706028

DO - 10.1083/jcb.200706028

M3 - Journal article

C2 - 18332216

SN - 0021-9525

VL - 180

SP - 897

EP - 904

JO - Journal of Cell Biology

JF - Journal of Cell Biology

IS - 5

ER -