Journal
NATURE IMMUNOLOGY
Volume 14, Issue 7, Pages 756-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.2615
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Funding
- Swiss National Science Foundation
- Roche
- Fondation Suisse pour les Bourses en Medecine et Biologie
- Swedish Research Council
- Genome Canada (through the Ontario Genomics Institute)
- Ontario Institute for Cancer Research
- province of Ontario
- Canadian Institutes for Health Research
- Canada Research Chairs Program
- Princess Margaret Hospital Foundation
- Terry Fox Research Institute
- Canadian Cancer Society Research Institute
- Ontario Ministry of Health and Long Term Care
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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.
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