Project description:To identify the “time-lapse” TF networks during B lineage commitment, we established multipotent progenitors harboring a tamoxifen-inducible form of Id3, an in vitro system where virtually all cells became B cells within 6 days by simply withdrawing 4-OHT. In this study, single cell transcriptomic analysis at pre- and post-commitment was performed using the culture system. In addition, we also performed single cell RNA-seq analysis of B cell precursor populations (LMPP, CLP and pro-B cells) in murine bone marrow.
Project description:Single cell studies elucidating the transcriptional continuum underpinning lineage commitment in the human bone marrow (BM) have advanced the understanding of hematopoiesis beyond the classic hierarchical model. However, T-lineage commitment, which occurs in the thymus remains incompletely defined. We mapped single cell transcriptomes spanning post-natal human thymopoiesis including the earliest progenitors. Instead of previously described discrete populations, transcriptional and lineage assay data resolved a continuum of novel cell states within CD34+ thymic progenitor cells. The initial stages of thymopoiesis involve multilineage priming of single cells followed by a gradual transition to T-commitment, a continuum previously undescribed outside the BM. Early progenitors express a hematopoietic stem cell (HSC) like profile but unlike HSC show initiation of T-priming. Species related differences exist in the earliest progenitor cells.