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Transcriptome changes affecting Hedgehog and cytokine signalling in the umbilical cord: implications for disease risk

Transcriptome changes affecting Hedgehog and cytokine signalling in the umbilical cord: implications for disease risk
Transcriptome changes affecting Hedgehog and cytokine signalling in the umbilical cord: implications for disease risk
BACKGROUND: Babies born at lower gestational ages or smaller birthweights have a greater risk of poorer health in later life. Both the causes of these sub-optimal birth outcomes and the mechanism by which the effects are transmitted over decades are the subject of extensive study. We investigated whether a transcriptomic signature of either birthweight or gestational age could be detected in umbilical cord RNA.

METHODS: The gene expression patterns of 32 umbilical cords from Singaporean babies of Chinese ethnicity across a range of birthweights (1698-4151 g) and gestational ages (35-41 weeks) were determined. We confirmed the differential expression pattern by gestational age for 12 genes in a series of 127 umbilical cords of Chinese, Malay and Indian ethnicity.

RESULTS: We found that the transcriptome is substantially influenced by gestational age; but less so by birthweight. We show that some of the expression changes dependent on gestational age are enriched in signal transduction pathways, such as Hedgehog and in genes with roles in cytokine signalling and angiogenesis. We show that some of the gene expression changes we report are reflected in the epigenome.

CONCLUSIONS: We studied the umbilical cord which is peripheral to disease susceptible tissues. The results suggest that soma-wide transcriptome changes, preserved at the epigenetic level, may be a mechanism whereby birth outcomes are linked to the risk of adult metabolic and arthritic disease and suggest that greater attention be given to the association between premature birth and later disease risk.
1932-6203
e39744
Stunkel, W.
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Pan, H.
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Chew, S.B.
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Tng, E.
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Tan, J.H.
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Chen, L.
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Joseph, R.
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Cheong, C.Y.
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Ong, M.L.
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Lee, Y.S.
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Chong, Y.S.
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Saw, S.M.
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Meaney, M.J.
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Kwek, K.
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Sheppard, A.M.
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Gluckman, P.D.
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Holbrook, J.D.
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Bier, D.
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Biswas, A.
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Shirong, C.
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Chan, H.
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Chee, C.
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Chia, A.
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Cutfield, W.
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Ming, D.C.
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Godfrey, K.M.
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Hartman, M.
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Heymann, M.
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Chin-Ying, S.H.
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Inskip, H.
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Kapur, J.
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Magiati, I.
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Morton, S.
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Krishnamoorthy, N.
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Ngo, C.
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Wei, P.W.
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Agarwal, P.
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Long, Q.B.
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Rajadurai, V.S.
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Richmond, J.
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Sheppard, A.
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Shek, L.P.
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Shuter, B.
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Singh, L.
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Wing Chee, S.
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Soh Shu, E.
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Lin, S.L.
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Hian, T.K.
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Hoe, T.O.
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Tong, T.Y.
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Tint, M.T.
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Van Bever, H.
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Van Dam, R.
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Venkatesh, S.
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Verkooijen, H.M.
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Wong, I.B.
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Wong, P.C.
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Yap, F.
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Yeo, G.S.
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Stunkel, W.
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Pan, H.
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Chew, S.B.
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Tng, E.
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Tan, J.H.
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Chen, L.
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Joseph, R.
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Cheong, C.Y.
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Ong, M.L.
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Lee, Y.S.
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Chong, Y.S.
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Saw, S.M.
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Meaney, M.J.
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Kwek, K.
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Sheppard, A.M.
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Gluckman, P.D.
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Holbrook, J.D.
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Bier, D.
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Biswas, A.
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Shirong, C.
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Chan, H.
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Chan, J.
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Chan, Y.H.
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Chee, C.
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Chia, A.
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Chin, C.W.
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Chinnadurai, A.
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Kiat, C.C.
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Chong, M.
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Chee, C.S.
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Chien, C.M.
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Cutfield, W.
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Daniel, M.
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Ming, D.C.
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Godfrey, K.M.
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Ferguson-Smith, A.
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Finkelstein, E.A.
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Fortier, M.
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Fok, D.
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Goh, A.
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Goh, D.
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Gooley, J.J.
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Meng, H.W.
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Hanson, M.
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Hartman, M.
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Heymann, M.
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Chin-Ying, S.H.
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Inskip, H.
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Kapur, J.
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Wah, L.B.
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Seng, L.Y.
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Leutscher-Broekman, B.F.
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Feei, L.S.
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Ling, L.Y.
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Magiati, I.
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Morton, S.
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Krishnamoorthy, N.
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Ngo, C.
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Wei, P.W.
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Agarwal, P.
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Anqi, Q.
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Long, Q.B.
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Rajadurai, V.S.
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Richmond, J.
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Shuter, B.
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Venkatesh, S.
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Verkooijen, H.M.
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Wong, P.C.
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Yap, F.
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Yeo, G.S.
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Stunkel, W., Pan, H., Chew, S.B., Tng, E., Tan, J.H., Chen, L., Joseph, R., Cheong, C.Y., Ong, M.L., Lee, Y.S., Chong, Y.S., Saw, S.M., Meaney, M.J., Kwek, K., Sheppard, A.M., Gluckman, P.D., Holbrook, J.D., Bier, D., Biswas, A., Shirong, C., Chan, H., Chan, J., Chan, Y.H., Chee, C., Chia, A., Chin, C.W., Chinnadurai, A., Kiat, C.C., Chong, M., Chee, C.S., Chien, C.M., Cutfield, W., Daniel, M., Ming, D.C., Godfrey, K.M., Ferguson-Smith, A., Finkelstein, E.A., Fortier, M., Fok, D., Goh, A., Goh, D., Gooley, J.J., Meng, H.W., Hanson, M., Hartman, M., Heymann, M., Chin-Ying, S.H., Inskip, H., Kapur, J., Wah, L.B., Seng, L.Y., Leutscher-Broekman, B.F., Bee, L.S., Feei, L.S., Ling, L.Y., Magiati, I., Morton, S., Krishnamoorthy, N., Ngo, C., Wei, P.W., Agarwal, P., Anqi, Q., Long, Q.B., Rajadurai, V.S., Richmond, J., Rifkin-Graboi, A., Sheppard, A., Shek, L.P., Shuter, B., Singh, L., Wing Chee, S., Soh Shu, E., Lin, S.L., Hian, T.K., Hui, T.S., Hoe, T.O., Tong, T.Y., Tint, M.T., Van Bever, H., Van Dam, R., Venkatesh, S., Verkooijen, H.M., Wong, I.B., Wong, P.C., Yap, F. and Yeo, G.S. (2012) Transcriptome changes affecting Hedgehog and cytokine signalling in the umbilical cord: implications for disease risk. PLoS ONE, 7 (7), e39744. (doi:10.1371/journal.pone.0039744). (PMID:22808055)

Record type: Article

Abstract

BACKGROUND: Babies born at lower gestational ages or smaller birthweights have a greater risk of poorer health in later life. Both the causes of these sub-optimal birth outcomes and the mechanism by which the effects are transmitted over decades are the subject of extensive study. We investigated whether a transcriptomic signature of either birthweight or gestational age could be detected in umbilical cord RNA.

METHODS: The gene expression patterns of 32 umbilical cords from Singaporean babies of Chinese ethnicity across a range of birthweights (1698-4151 g) and gestational ages (35-41 weeks) were determined. We confirmed the differential expression pattern by gestational age for 12 genes in a series of 127 umbilical cords of Chinese, Malay and Indian ethnicity.

RESULTS: We found that the transcriptome is substantially influenced by gestational age; but less so by birthweight. We show that some of the expression changes dependent on gestational age are enriched in signal transduction pathways, such as Hedgehog and in genes with roles in cytokine signalling and angiogenesis. We show that some of the gene expression changes we report are reflected in the epigenome.

CONCLUSIONS: We studied the umbilical cord which is peripheral to disease susceptible tissues. The results suggest that soma-wide transcriptome changes, preserved at the epigenetic level, may be a mechanism whereby birth outcomes are linked to the risk of adult metabolic and arthritic disease and suggest that greater attention be given to the association between premature birth and later disease risk.

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e-pub ahead of print date: 10 July 2012
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 348476
URI: http://eprints.soton.ac.uk/id/eprint/348476
DOI: doi:10.1371/journal.pone.0039744
ISSN: 1932-6203
PURE UUID: f9022bcd-898f-4416-8687-1934f414c385
ORCID for K.M. Godfrey: ORCID iD orcid.org/0000-0002-4643-0618
ORCID for M. Hanson: ORCID iD orcid.org/0000-0002-6907-613X
ORCID for H. Inskip: ORCID iD orcid.org/0000-0001-8897-1749

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Date deposited: 14 Feb 2013 12:18
Last modified: 15 Mar 2024 03:07

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Contributors

Author: W. Stunkel
Author: H. Pan
Author: S.B. Chew
Author: E. Tng
Author: J.H. Tan
Author: L. Chen
Author: R. Joseph
Author: C.Y. Cheong
Author: M.L. Ong
Author: Y.S. Lee
Author: Y.S. Chong
Author: S.M. Saw
Author: M.J. Meaney
Author: K. Kwek
Author: A.M. Sheppard
Author: P.D. Gluckman
Author: J.D. Holbrook
Author: D. Bier
Author: A. Biswas
Author: C. Shirong
Author: H. Chan
Author: J. Chan
Author: Y.H. Chan
Author: C. Chee
Author: A. Chia
Author: C.W. Chin
Author: A. Chinnadurai
Author: C.C. Kiat
Author: M. Chong
Author: C.S. Chee
Author: C.M. Chien
Author: W. Cutfield
Author: M. Daniel
Author: D.C. Ming
Author: K.M. Godfrey ORCID iD
Author: A. Ferguson-Smith
Author: E.A. Finkelstein
Author: M. Fortier
Author: D. Fok
Author: A. Goh
Author: D. Goh
Author: J.J. Gooley
Author: H.W. Meng
Author: M. Hanson ORCID iD
Author: M. Hartman
Author: M. Heymann
Author: S.H. Chin-Ying
Author: H. Inskip ORCID iD
Author: J. Kapur
Author: L.B. Wah
Author: L.Y. Seng
Author: B.F. Leutscher-Broekman
Author: L.S. Bee
Author: L.S. Feei
Author: L.Y. Ling
Author: I. Magiati
Author: S. Morton
Author: N. Krishnamoorthy
Author: C. Ngo
Author: P.W. Wei
Author: P. Agarwal
Author: Q. Anqi
Author: Q.B. Long
Author: V.S. Rajadurai
Author: J. Richmond
Author: A. Rifkin-Graboi
Author: A. Sheppard
Author: L.P. Shek
Author: B. Shuter
Author: L. Singh
Author: S. Wing Chee
Author: E. Soh Shu
Author: S.L. Lin
Author: T.K. Hian
Author: T.S. Hui
Author: T.O. Hoe
Author: T.Y. Tong
Author: M.T. Tint
Author: H. Van Bever
Author: R. Van Dam
Author: S. Venkatesh
Author: H.M. Verkooijen
Author: I.B. Wong
Author: P.C. Wong
Author: F. Yap
Author: G.S. Yeo

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