Negative regulation of lymphoid specification by the transcription factor TAL1
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE126402 | GEO | 2019/02/12
REPOSITORIES: GEO
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Project description:A classical view of blood cell development is that multipotent haematopoietic stem and progenitor cells (HSPCs) become lineage-restricted at defined stages. The Lin–c-kit+Sca1+Flt3+ stage, termed lymphoid-primed multipotent progenitors (LMPPs), have lost megakaryocyte and erythroid potential but are heterogeneous in their fate. Through single cell RNA-sequencing, we identify heterogeneous expression of Dach1 and associated genes in this fraction where it co-expressed 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– subpopulation within LMPPs with lymphoid potential but devoid of myeloid potential. We term these ‘lymphoid-primed progenitors’, or LPPs. These findings define the earliest branch point of lymphoid development in haematopoiesis and a means for their prospective isolation.
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2012-06-13 | E-GEOD-38681 | biostudies-arrayexpress
Project description:Despite recent advances in the identification of lymphoid-restricted progenitors, the transcription factors essential for their generation remain to be identified. Here we describe an unexpected role for the myeloid oncogene Mef2c in multipotent progenitors (MPPs), where it is required for pan-lymphoid differentiation. Mef2c deficiency was associated with profound defects in B, T, NK cell and common lymphoid progenitor production and an enhanced myeloid output. Mef2c deficiency in MPPs leads to downregulation of several key lymphoid regulators and the upregulation of the myeloid factor C/EBPa. Our studies also show that Mef2c is a critical transcriptional target of PU.1 during lymphopoiesis. Thus, Mef2c is a crucial component of the transcriptional network that regulates lymphoid specification and cell fate choice in MPPs.
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Project description:A classical view of blood cell development is that multipotent haematopoietic stem and progenitor cells (HSPCs) become lineage-restricted at defined stages. The Lin–c-kit+Sca1+Flt3+ stage, termed lymphoid-primed multipotent progenitors (LMPPs), have lost megakaryocyte and erythroid potential but are heterogeneous in their fate. Through single cell RNA-sequencing, we identify heterogeneous expression of Dach1 and associated genes in this fraction where it co-expressed 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– subpopulation within LMPPs with lymphoid potential but devoid of myeloid potential. We term these ‘lymphoid-primed progenitors’, or LPPs. These findings define the earliest branch point of lymphoid development in haematopoiesis and a means for their prospective isolation.
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Project description:Lyl-1 knockout vs wildtype Lymphoid Primed Multipotent Progenitors (LMPPs)
| PRJNA168481 | ENA