Single-cell transcriptomics dissects the transcriptome alterations of hematopoietic stem cells in myelodysplastic neoplasms.

BACKGROUND: Myelodysplastic neoplasms (MDS) are myeloid neoplasms characterized by disordered differentiation of hematopoietic stem cells and a predisposition to acute myeloid leukemia (AML). The underline pathogenesis remains unclear. METHODS: In this study, the trajectory of differentiation and mechanisms of leukemic transformation were explored through bioinformatics analysis of single-cell RNA-Seq data from hematopoietic stem and progenitor cells (HSPCs) in MDS patients. RESULTS: Among the HSPC clusters, the proportion of common myeloid progenitor (CMP) was the main cell cluster in the patients with excess blasts (EB)/ secondary AML. Cell cycle analysis indicated the CMP of MDS patients were in an active proliferative state. The genes involved in the cell proliferation, such as MAML3 and PLCB1, were up-regulated in MDS CMP. Further validation analysis indicated that the expression levels of MAML3 and PLCB1 in patients with MDS-EB were significantly higher than those without EB. Patients with high expression of PLCB1 had a higher risk of transformation to AML. PLCB1 inhibitor can suppress proliferation, induce cell cycle arrest, and activate apoptosis of leukemic cells in vitro. CONCLUSION: This study revealed the transcriptomic change of HSPCs in MDS patients along the pseudotime and indicated that PLCB1 plays a key role in the transformation of MDS into leukemia.

[Change of T lymphocyte and its activated subsets in SARS patients].

OBJECTIVE: To study abnormal changes of T lymphocyte and its activated subsets in severe acute respiratory syndrome (SARS) patients. METHODS: Flow cytometer with multi-color flouroscence and hematology analyzer were used to detect the expression of T lymphocyte and its activated a subsets in 240 SARS patients including 50 cases of critical type and 190 cases of common type. RESULTS: Statistical analysis by means of SAS software showed that there was significant decrease in absolute counts (AC) of T lymphocyte and its subsets in SARS patients when compared with normal people, while percentages (PC) of CD3+CD25+ and CD3+ HLA-DR+ subsets were increased markedly. Compared with common type, there was significant decrease in absolute counts of critical type of T lymphocyte, CD4+, CD25+CD3+, CD28+CD4+, and CD95+CD4+subsets. The ACs of T lymphocytes including CD4 and CD8 subsets in different phases were as below: III > II > I. The ACs of subsets involved in activation such as CD3+ HLA-DR+/lym, CD3+CD25+/lym, CD28+CD4+/CD4, CD28+CD8+/CD8, and CD38+CD4+/CD4 all were highest in group III. In addition, the AC and PC of CD95+CD4+/CD4 and CD95+CD8/CD8 subset in group III were highest while group I was lowest. CONCLUSIONS: With depressing cellular immunity, the activation of T lymphocytes were suppressed obviously in SARS patients, especially for critical patients.