title: Identification of transcriptional regulators in the mouse immune system.
abstract: The differentiation of hematopoietic stem cells into cells of the immune system has been studied extensively in mammals, but the transcriptional circuitry that controls it is still only partially understood. Here, the Immunological Genome Project gene-expression profiles across mouse immune lineages allowed us to systematically analyze these circuits. To analyze this data set we developed Ontogenet, an algorithm for reconstructing lineage-specific regulation from gene-expression profiles across lineages. Using Ontogenet, we found differentiation stage-specific regulators of mouse hematopoiesis and identified many known hematopoietic regulators and 175 previously unknown candidate regulators, as well as their target genes and the cell types in which they act. Among the previously unknown regulators, we emphasize the role of ETV5 in the differentiation of γδ T cells. As the transcriptional programs of human and mouse cells are highly conserved, it is likely that many lessons learned from the mouse model apply to humans.
authors.affiliation: Computer Science Department, Stanford University, Stanford, California, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Jojic
authors.forename: Tal
authors.initials: T
authors.lastname: Shay
authors.forename: Katelyn
authors.initials: K
authors.lastname: Sylvia
authors.forename: Or
authors.initials: O
authors.lastname: Zuk
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.forename: Joonsoo
authors.initials: J
authors.lastname: Kang
authors.forename: Aviv
authors.initials: A
authors.lastname: Regev
authors.forename: Daphne
authors.initials: D
authors.lastname: Koller
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Best
authors.forename: Jamie
authors.initials: J
authors.lastname: Knell
authors.forename: Ananda
authors.initials: A
authors.lastname: Goldrath
authors.forename: Vladimir
authors.initials: V
authors.lastname: Joic
authors.forename: Daphne
authors.initials: D
authors.lastname: Koller
authors.forename: Tal
authors.initials: T
authors.lastname: Shay
authors.forename: Aviv
authors.initials: A
authors.lastname: Regev
authors.forename: Nadia
authors.initials: N
authors.lastname: Cohen
authors.forename: Patrick
authors.initials: P
authors.lastname: Brennan
authors.forename: Michael
authors.initials: M
authors.lastname: Brenner
authors.forename: Francis
authors.initials: F
authors.lastname: Kim
authors.forename: Tata Nageswara
authors.initials: TN
authors.lastname: Rao
authors.forename: Amy
authors.initials: A
authors.lastname: Wagers
authors.forename: Tracy
authors.initials: T
authors.lastname: Heng
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Ericson
authors.forename: Katherine
authors.initials: K
authors.lastname: Rothamel
authors.forename: Adriana
authors.initials: A
authors.lastname: Ortiz-Lopez
authors.forename: Diane
authors.initials: D
authors.lastname: Mathis
authors.forename: Christophe
authors.initials: C
authors.lastname: Benoist
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Bezman
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Sun
authors.forename: Gundula
authors.initials: G
authors.lastname: Min-Oo
authors.forename: Charlie C
authors.initials: CC
authors.lastname: Kim
authors.forename: Lewis L
authors.initials: LL
authors.lastname: Lanier
authors.forename: Jennifer
authors.initials: J
authors.lastname: Miller
authors.forename: Brian
authors.initials: B
authors.lastname: Brown
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
authors.forename: Emmanuel L
authors.initials: EL
authors.lastname: Gautier
authors.forename: Claudia
authors.initials: C
authors.lastname: Jakubzick
authors.forename: Gwendalyn J
authors.initials: GJ
authors.lastname: Randolph
authors.forename: Paul
authors.initials: P
authors.lastname: Monach
authors.forename: David A
authors.initials: DA
authors.lastname: Blair
authors.forename: Michael L
authors.initials: ML
authors.lastname: Dustin
authors.forename: Susan A
authors.initials: SA
authors.lastname: Shinton
authors.forename: Richard R
authors.initials: RR
authors.lastname: Hardy
authors.forename: David
authors.initials: D
authors.lastname: Laidlaw
authors.forename: Jim
authors.initials: J
authors.lastname: Collins
authors.forename: Roi
authors.initials: R
authors.lastname: Gazit
authors.forename: Derrick J
authors.initials: DJ
authors.lastname: Rossi
authors.forename: Nidhi
authors.initials: N
authors.lastname: Malhotra
authors.forename: Katelyn
authors.initials: K
authors.lastname: Sylvia
authors.forename: Joonsoo
authors.initials: J
authors.lastname: Kang
authors.forename: Taras
authors.initials: T
authors.lastname: Kreslavsky
authors.forename: Anne
authors.initials: A
authors.lastname: Fletcher
authors.forename: Kutlu
authors.initials: K
authors.lastname: Elpek
authors.forename: Angelique
authors.initials: A
authors.lastname: Bellemarte-Pelletier
authors.forename: Deepali
authors.initials: D
authors.lastname: Malhotra
authors.forename: Shannon
authors.initials: S
authors.lastname: Turley
mesh_terms: D000465:Algorithms; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology*; D053263:Gene Regulatory Networks / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology*; D059467:Transcriptome / Q000235:genetics / Q000276:immunology
chemical_list: D004268:DNA-Binding Proteins; C513242:Etv5 protein, mouse; D016692:Receptors, Antigen, T-Cell, gamma-delta; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors