Zusammenfassung
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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