【摘 要】
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Whereas the critical roles of innate lymphoid cells (ILCs) in adult are increasingly appreciated,their developmental hierarchy in early human fetus remains largely elusive.In this study,we sorted human hematopoietic stem/progenitor cells,lymphoid progenit
【机 构】
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State Key Laboratory of Proteomics,Academy of Military Medical Sciences,Academy of Military Sciences
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Whereas the critical roles of innate lymphoid cells (ILCs) in adult are increasingly appreciated,their developmental hierarchy in early human fetus remains largely elusive.In this study,we sorted human hematopoietic stem/progenitor cells,lymphoid progenitors,putative ILC progenitor/precursors and mature ILCs in the fetal hematopoietic,lymphoid and non-lymphoid tissues,from 8 to 12 post-conception weeks,for single-cell RNA-sequencing,followed by computational analysis and functional validation at bulk and single-cell levels.We delineated the early phase of ILC lineage commitment from hematopoietic stem/progenitor cells,which mainly occurred in fetal liver and intestine.We further unveiled interleukin-3 receptor as a surface marker for the lymphoid progenitors in fetal liver with T,B,ILC and myeloid potentials,while IL-3RA-lymphoid progenitors were predominantly B-lineage committed.Notably,we determined the heterogeneity and tissue distribution of each ILC subpopulation,revealing the proliferating characteristics shared by the precursors of each ILC subtype.Additionally,a novel unconventional ILC2 subpopulation (CRTH2-CCR9+ ILC2) was identified in fetal thymus.Taken together,our study illuminates the precise cellular and molecular features underlying the stepwise formation of human fetal ILC hierarchy with remarkable spatiotemporal heterogeneity.
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