1Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire 03756, USA;
2Department of Neurological Surgery, Institute for Human Genetics, University of California San Francisco, San Francisco, California
94158, USA;
3Department of Biostatistics, University of Kansas Medical Center, Kansas City, Kansas 66160, USA;
4Department of Epidemiology, Brown University, Providence, Rhode Island 02912, USA;
5Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island 02912, USA;
6Department of Molecular and Systems Biology, Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire 03756, USA;
7Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire 03756, USA
↵8 These authors contributed equally to this work.
↵9 These authors contributed equally to this work.
Corresponding author: john.wiencke{at}ucsf.edu
Abstract
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.
Footnotes
[Supplemental material is available for this article.]
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at https://creativecommons.org/licenses/by-nc/4.0/.
