title: The transcriptional architecture of early human hematopoiesis identifies multilevel control of lymphoid commitment.
abstract: Understanding how differentiation programs originate from the gene-expression 'landscape' of hematopoietic stem cells (HSCs) is crucial for the development of new clinical therapies. We mapped the transcriptional dynamics underlying the first steps of commitment by tracking transcriptome changes in human HSCs and eight early progenitor populations. We found that transcriptional programs were extensively shared, extended across lineage-potential boundaries and were not strictly lineage affiliated. Elements of stem, lymphoid and myeloid programs were retained in multilymphoid progenitors (MLPs), which reflected a hybrid transcriptional state. By functional single cell analysis, we found that the transcription factors Bcl-11A, Sox4 and TEAD1 (TEF1) governed transcriptional networks in MLPs, which led to B cell specification. Overall, we found that integrated transcriptome approaches can be used to identify previously unknown regulators of multipotency and show additional complexity in lymphoid commitment.
authors.affiliation: Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Elisa
authors.initials: E
authors.lastname: Laurenti
authors.forename: Sergei
authors.initials: S
authors.lastname: Doulatov
authors.forename: Sasan
authors.initials: S
authors.lastname: Zandi
authors.forename: Ian
authors.initials: I
authors.lastname: Plumb
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Craig
authors.initials: C
authors.lastname: April
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Fan
authors.forename: John E
authors.initials: JE
authors.lastname: Dick
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage; D019295:Computational Biology; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D014157:Transcription Factors