A new lymphoid-primed progenitor marked by Dach1 downregulation identified with single cell multi-omics.
Daniela Amann-ZalcensteinLu-Yi TianJaring SchreuderSara TomeiDawn S LinKirsten A FairfaxJessica E BoldenMark D McKenzieAndrew JarrattAdrienne HiltonJacob T JacksonLadina Di RagoMatthew P McCormackCarolyn A de GraafOlivia StonehouseSamir TaoudiWarren S AlexanderStephen L NuttMatthew E RitchieAshley P NgShalin H NaikPublished in: Nature immunology (2020)
A classical view of blood cell development is that multipotent hematopoietic stem and progenitor cells (HSPCs) become lineage-restricted at defined stages. Lin-c-Kit+Sca-1+Flt3+ cells, termed lymphoid-primed multipotent progenitors (LMPPs), have lost megakaryocyte and erythroid potential but are heterogeneous in their fate. Here, through single-cell RNA sequencing, we identify the expression of Dach1 and associated genes in this fraction as being coexpressed with myeloid/stem genes but inversely correlated with lymphoid genes. Through generation of Dach1-GFP reporter mice, we identify a transcriptionally and functionally unique Dach1-GFP- subpopulation within LMPPs with lymphoid potential with low to negligible classic myeloid potential. We term these 'lymphoid-primed progenitors' (LPPs). These findings define an early definitive branch point of lymphoid development in hematopoiesis and a means for prospective isolation of LPPs.
Keyphrases
- single cell
- rna seq
- acute myeloid leukemia
- genome wide
- high throughput
- poor prognosis
- induced apoptosis
- bone marrow
- cell proliferation
- dna methylation
- stem cells
- radiation therapy
- skeletal muscle
- human health
- gene expression
- adipose tissue
- metabolic syndrome
- cell death
- transcription factor
- risk assessment
- long non coding rna
- oxidative stress
- type diabetes
- binding protein
- preterm birth
- cell fate