%0 Journal Article %1 Laurenti2013transcriptionalarchitectureof %A Laurenti, Elisa %A Doulatov, Sergei %A Zandi, Sasan %A Plumb, Ian %A Chen, Jing %A April, Craig %A Fan, Jian-Bing %A Dick, John E %D 2013 %J Nat Immunol %K imported %N 7 %P 756--763 %R 10.1038/ni.2615 %T The transcriptional architecture of early human hematopoiesis identifies multilevel control of lymphoid commitment. %U http://dx.doi.org/10.1038/ni.2615 %V 14 %X 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.

@article{Laurenti2013transcriptionalarchitectureof, 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.}, added-at = {2014-05-13T15:48:44.000+0200}, author = {Laurenti, Elisa and Doulatov, Sergei and Zandi, Sasan and Plumb, Ian and Chen, Jing and April, Craig and Fan, Jian-Bing and Dick, John E}, biburl = {https://www.bibsonomy.org/bibtex/20f5c9794afdc9f4c9fef9d12daf8a15e/gwotto}, doi = {10.1038/ni.2615}, file = {Laurenti2013transcriptionalarchitectureof.pdf:Laurenti2013transcriptionalarchitectureof.pdf:PDF;:/home/gotto/references/library/supplementary data/Laurenti2013transcriptionalarchitectureof-sd.pdf:PDF}, institution = {Cancer Research{\,} Ontario Cancer Institute{\,} Princess Margaret Cancer Centre{\,} University Health Network{\,} Toronto{\,} Ontario{\,} Canada.}, interhash = {37fb295f45aaed05d615fc38e3f857d3}, intrahash = {0f5c9794afdc9f4c9fef9d12daf8a15e}, journal = {Nat Immunol}, keywords = {imported}, language = {eng}, medline-pst = {ppublish}, month = May, number = 7, owner = {gotto}, pages = {756--763}, pii = {ni.2615}, pmid = {23708252}, timestamp = {2014-05-13T15:48:44.000+0200}, title = {The transcriptional architecture of early human hematopoiesis identifies multilevel control of lymphoid commitment.}, url = {http://dx.doi.org/10.1038/ni.2615}, volume = 14, year = 2013 }