title: De Novo Prediction of Stem Cell Identity using Single-Cell Transcriptome Data.
abstract: Adult mitotic tissues like the intestine, skin, and blood undergo constant turnover throughout the life of an organism. Knowing the identity of the stem cell is crucial to understanding tissue homeostasis and its aberrations upon disease. Here we present a computational method for the derivation of a lineage tree from single-cell transcriptome data. By exploiting the tree topology and the transcriptome composition, we establish StemID, an algorithm for identifying stem cells among all detectable cell types within a population. We demonstrate that StemID recovers two known adult stem cell populations, Lgr5+ cells in the small intestine and hematopoietic stem cells in the bone marrow. We apply StemID to predict candidate multipotent cell populations in the human pancreas, a tissue with largely uncharacterized turnover dynamics. We hope that StemID will accelerate the search for novel stem cells by providing concrete markers for biological follow-up and validation.
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, 3584 CT Utrecht, the Netherlands; Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands; Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany. Electronic address: gruen@ie-freibug.mpg.de.
authors.forename: Dominic
authors.initials: D
authors.lastname: Grün
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, 3584 CT Utrecht, the Netherlands; Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.
authors.forename: Mauro J
authors.initials: MJ
authors.lastname: Muraro
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, 3584 CT Utrecht, the Netherlands; Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Boisset
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, 3584 CT Utrecht, the Netherlands; Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.
authors.forename: Kay
authors.initials: K
authors.lastname: Wiebrands
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, 3584 CT Utrecht, the Netherlands; Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.
authors.forename: Anna
authors.initials: A
authors.lastname: Lyubimova
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, 3584 CT Utrecht, the Netherlands; Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands; Department of Medicine, Section of Nephrology and Section of Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
authors.forename: Gitanjali
authors.initials: G
authors.lastname: Dharmadhikari
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, 3584 CT Utrecht, the Netherlands; Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.
authors.forename: Maaike
authors.initials: M
authors.lastname: van den Born
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, 3584 CT Utrecht, the Netherlands; Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: van Es
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, 3584 CT Utrecht, the Netherlands; Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Jansen
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, 3584 CT Utrecht, the Netherlands; Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands; Princess Maxima Center for Pediatric Oncology, 3508 AB Utrecht, the Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, 3584 CT Utrecht, the Netherlands; Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands; Department of Medicine, Section of Nephrology and Section of Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
authors.forename: Eelco J P
authors.initials: EJP
authors.lastname: de Koning
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, 3584 CT Utrecht, the Netherlands; Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands. Electronic address: a.vanoudenaarden@hubrecht.eu.
authors.forename: Alexander
authors.initials: A
authors.lastname: van Oudenaarden
mesh_terms: D000328:Adult; D000465:Algorithms; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D019070:Cell Lineage; D019277:Entropy; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007422:Intestines / Q000166:cytology; D008810:Mice, Inbred C57BL; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism; D010183:Pancreatic Ducts / Q000166:cytology; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D015203:Reproducibility of Results; D059010:Single-Cell Analysis / Q000379:methods*; D013234:Stem Cells / Q000166:cytology*; D059467:Transcriptome / Q000235:genetics*