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Tracing human stem cell lineage during development using DNA methylation

Stem cell maturation is a fundamental, yet poorly understood aspect of human development. We devised a DNA methylation signature deeply reminiscent of embryonic stem cells (a fetal cell origin signature, FCO) to interrogate the evolving character of multiple human tissues. The cell fraction displayi...

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Detalles Bibliográficos
Autores principales: Salas, Lucas A., Wiencke, John K., Koestler, Devin C., Zhang, Ze, Christensen, Brock C., Kelsey, Karl T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120629/
https://www.ncbi.nlm.nih.gov/pubmed/30072366
http://dx.doi.org/10.1101/gr.233213.117
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author Salas, Lucas A.
Wiencke, John K.
Koestler, Devin C.
Zhang, Ze
Christensen, Brock C.
Kelsey, Karl T.
author_facet Salas, Lucas A.
Wiencke, John K.
Koestler, Devin C.
Zhang, Ze
Christensen, Brock C.
Kelsey, Karl T.
author_sort Salas, Lucas A.
collection PubMed
description Stem cell maturation is a fundamental, yet poorly understood aspect of human development. We devised a DNA methylation signature deeply reminiscent of embryonic stem cells (a fetal cell origin signature, FCO) to interrogate the evolving character of multiple human tissues. The cell fraction displaying this FCO signature was highly dependent upon developmental stage (fetal versus adult), and in leukocytes, it described a dynamic transition during the first 5 yr of life. Significant individual variation in the FCO signature of leukocytes was evident at birth, in childhood, and throughout adult life. The genes characterizing the signature included transcription factors and proteins intimately involved in embryonic development. We defined and applied a DNA methylation signature common among human fetal hematopoietic progenitor cells and have shown that this signature traces the lineage of cells and informs the study of stem cell heterogeneity in humans under homeostatic conditions.
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spelling pubmed-61206292018-09-05 Tracing human stem cell lineage during development using DNA methylation Salas, Lucas A. Wiencke, John K. Koestler, Devin C. Zhang, Ze Christensen, Brock C. Kelsey, Karl T. Genome Res Research Stem cell maturation is a fundamental, yet poorly understood aspect of human development. We devised a DNA methylation signature deeply reminiscent of embryonic stem cells (a fetal cell origin signature, FCO) to interrogate the evolving character of multiple human tissues. The cell fraction displaying this FCO signature was highly dependent upon developmental stage (fetal versus adult), and in leukocytes, it described a dynamic transition during the first 5 yr of life. Significant individual variation in the FCO signature of leukocytes was evident at birth, in childhood, and throughout adult life. The genes characterizing the signature included transcription factors and proteins intimately involved in embryonic development. We defined and applied a DNA methylation signature common among human fetal hematopoietic progenitor cells and have shown that this signature traces the lineage of cells and informs the study of stem cell heterogeneity in humans under homeostatic conditions. Cold Spring Harbor Laboratory Press 2018-09 /pmc/articles/PMC6120629/ /pubmed/30072366 http://dx.doi.org/10.1101/gr.233213.117 Text en © 2018 Salas et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research
Salas, Lucas A.
Wiencke, John K.
Koestler, Devin C.
Zhang, Ze
Christensen, Brock C.
Kelsey, Karl T.
Tracing human stem cell lineage during development using DNA methylation
title Tracing human stem cell lineage during development using DNA methylation
title_full Tracing human stem cell lineage during development using DNA methylation
title_fullStr Tracing human stem cell lineage during development using DNA methylation
title_full_unstemmed Tracing human stem cell lineage during development using DNA methylation
title_short Tracing human stem cell lineage during development using DNA methylation
title_sort tracing human stem cell lineage during development using dna methylation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120629/
https://www.ncbi.nlm.nih.gov/pubmed/30072366
http://dx.doi.org/10.1101/gr.233213.117
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