A new lymphoid-primed progenitor marked by Dach1 downregulation identified with single cell multi-omics.

A new lymphoid-primed progenitor marked by Dach1 downregulation identified with single cell multi-omics.

Nature immunology (2020-10-21)

Daniela Amann-Zalcenstein, Luyi Tian, Jaring Schreuder, Sara Tomei, Dawn S Lin, Kirsten A Fairfax, Jessica E Bolden, Mark D McKenzie, Andrew Jarratt, Adrienne Hilton, Jacob T Jackson, Ladina Di Rago, Matthew P McCormack, Carolyn A de Graaf, Olivia Stonehouse, Samir Taoudi, Warren S Alexander, Stephen L Nutt, Matthew E Ritchie, Ashley P Ng, Shalin H Naik

PMID33077975

ABSTRACT

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.

MATERIALS

Product Number

Brand

Product Description

T2319

Sigma-Aldrich

Trizma^® hydrochloride solution, pH 7.5, BioPerformance Certified, 1 M, suitable for cell culture