title: Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors.
abstract: Within the bone marrow, stem cells differentiate and give rise to diverse blood cell types and functions. Currently, hematopoietic progenitors are defined using surface markers combined with functional assays that are not directly linked with in vivo differentiation potential or gene regulatory mechanisms. Here, we comprehensively map myeloid progenitor subpopulations by transcriptional sorting of single cells from the bone marrow. We describe multiple progenitor subgroups, showing unexpected transcriptional priming toward seven differentiation fates but no progenitors with a mixed state. Transcriptional differentiation is correlated with combinations of known and previously undefined transcription factors, suggesting that the process is tightly regulated. Histone maps and knockout assays are consistent with early transcriptional priming, while traditional transplantation experiments suggest that in vivo priming may still allow for plasticity given strong perturbations. These data establish a reference model and general framework for studying hematopoiesis at single-cell resolution.
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Franziska
authors.initials: F
authors.lastname: Paul
authors.affiliation: Department of Computer Science and Applied Mathematics and Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ya'ara
authors.initials: Y
authors.lastname: Arkin
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Amir
authors.initials: A
authors.lastname: Giladi
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Diego Adhemar
authors.initials: DA
authors.lastname: Jaitin
authors.affiliation: Department of Computer Science and Applied Mathematics and Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ephraim
authors.initials: E
authors.lastname: Kenigsberg
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Keren-Shaul
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Deborah
authors.initials: D
authors.lastname: Winter
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Lara-Astiaso
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Meital
authors.initials: M
authors.lastname: Gury
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Assaf
authors.initials: A
authors.lastname: Weiner
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: David
authors.affiliation: Department of Computer Science and Applied Mathematics and Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Nadav
authors.initials: N
authors.lastname: Cohen
authors.affiliation: The Finsen Laboratory, Rigshospitalet, University of Copenhagen, Copenhagen 2200, Denmark; Biotech Research and Innovation Centre (BRIC), Copenhagen 2200, Denmark; Danish Stem Cell Centre (DanStem) Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Felicia Kathrine Bratt
authors.initials: FK
authors.lastname: Lauridsen
authors.affiliation: Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Haas
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), BIOPOLIS 138648, Singapore; Genomics and Immunoregulation, Life and Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schlitzer
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Mildner
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), BIOPOLIS 138648, Singapore.
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Steffen
authors.initials: S
authors.lastname: Jung
authors.affiliation: Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Trumpp
authors.affiliation: The Finsen Laboratory, Rigshospitalet, University of Copenhagen, Copenhagen 2200, Denmark; Biotech Research and Innovation Centre (BRIC), Copenhagen 2200, Denmark; Danish Stem Cell Centre (DanStem) Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Bo Torben
authors.initials: BT
authors.lastname: Porse
authors.affiliation: Department of Computer Science and Applied Mathematics and Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: amos.tanay@weizmann.ac.il.
authors.forename: Amos
authors.initials: A
authors.lastname: Tanay
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: ido.amit@weizmann.ac.il.
authors.forename: Ido
authors.initials: I
authors.lastname: Amit
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D055786:Gene Knockout Techniques; D006410:Hematopoiesis; D059014:High-Throughput Nucleotide Sequencing; D051379:Mice; D008810:Mice, Inbred C57BL; D023461:Myeloid Progenitor Cells / Q000166:cytology* / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D059010:Single-Cell Analysis; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; D014157:Transcription Factors