Lin - PU.1 dim GATA-1 - defines haematopoietic stem cells with long-term multilineage reconstitution activity.
Haoyu XuShaojing TanYu ZhaoLin ZhangWeiyun CaoXing LiJiayi TianXiaojing WangXiaoyan LiFengchao WangJiani CaoTong-Biao ZhaoPublished in: Cell proliferation (2023)
Despite extensive characterization of the state and function of haematopoietic stem cells (HSCs), the use of transcription factors to define the HSC population is still limited. We show here that the HSC population in mouse bone marrow can be defined by the distinct expression levels of Spi1 and Gata1. By using a double fluorescence knock-in mouse model, PGdKI, in which the expression levels of PU.1 and GATA-1 are indicated by the expression of GFP and mCherry, respectively, we uncover that the HSCs with lymphoid and myeloid repopulating activity are specifically enriched in a Lin - PU.1 dim GATA-1 - (LPG) cell subset. In vivo competitive repopulation assays demonstrate that bone marrow cells gated by LPG exhibit haematopoietic reconstitution activity which is comparable to that of classical Lin - Sca1 + c-kit + (LSK). The integrated analysis of single-cell RNA sequence data from LPG and LSK-gated cells reveals that a transcriptional network governed by core TFs contributes to regulation of HSC multipotency. These discoveries provide new clues for HSC characterization and functional study.
Keyphrases
- transcription factor
- bone marrow
- stem cells
- poor prognosis
- single cell
- induced apoptosis
- mouse model
- mesenchymal stem cells
- cell cycle arrest
- dna binding
- cell therapy
- machine learning
- dendritic cells
- endoplasmic reticulum stress
- high throughput
- binding protein
- acute myeloid leukemia
- gene expression
- cell proliferation
- oxidative stress
- artificial intelligence
- single molecule
- network analysis
- genome wide identification
- electronic health record
- data analysis
- big data
- pi k akt