Volume 03 · Issue 02 · 2021

Bone marrow (BM) microenvironment regulates and supports the production of blood cells which are necessary to maintain homeostasis. In analogy to normal hematopoiesis, leukemogenesis is originated from leukemic stem cells (LSCs) which gives rise to more differentiated malignant cells. Leukemia cells occupy BM niches and reconstruct them to support leukemogenesis. The abnormal BM niches are the main sanctuary of LSCs where they can evade chemotherapy-induced death and acquire drug resistance. In this review, we focus on the protective effects of BM niche cells on acute lymphoblastic leukemia cells.

Single-cell RNA-seq data analysis generally requires quality control, normalization, highly variable genes screening, dimensionality reduction and clustering. Among these processes, downstream analysis including dimensionality reduction and clustering are sensitive to the selection of highly variable genes. Though increasing number of tools for selecting the highly variable genes have been developed, an evaluation of their performances and a general strategy are lack. Here, we compare the performance of nine commonly used methods for screening variable genes by using single-cell RNA-seq data from hematopoietic stem/progenitor cells and mature blood cells, and find that SCHS outperforms other methods regarding to reproducibility and accuracy. However, this method prefers the selection of highly expressed genes. We further propose a new strategy SIEVE (SIngle-cEll Variable gEnes) by multiple rounds of random sampling, therefore minimizing the stochastic noise and identifying a robust set of variable genes. Moreover, SIEVE recovers lowly expressed genes as variable genes and substantially improves the accuracy of single cell classification, especially for the methods with lower reproducibility. The SIEVE software is freely available at https://github.com/YinanZhang522/SIEVE.

GSDME contains a pore-forming domain at its N-terminal region to execute pyroptosis. Our previous study has reported that forced expression of Gsdme impairs the reconstitution capacity of hematopoietic stem cells (HSCs). While, how GSDME-mediated pyroptosis regulates HSCs remains unknown. Here, we show that hematopoietic stem and progenitor cells are capable to undergo pyroptosis in response to cisplatin treatment and GSDME is one of the genes mediating such process. Gsdme^-/- mice revealed no difference in the steady state of blood system while Gsdme^-/- HSCs exhibited compromised reconstitution capacity due to increased apoptosis. Briefly, this study reveals that GSDME modulates HSC function by coordinating pyroptosis and apoptosis.

Interleukin 34 (IL-34) is a cytokine that shares the receptor with colony-stimulating factor 1 (CSF-1). IL-34 is involved in a broad range of pathologic processes including cancer. We previously demonstrated that IL-34 promoted the proliferation and colony formation of human acute monocytic leukemia (AMoL) cells. However, the mechanism has not been elucidated. Here, by analyzing the gene profiles of Molm13 and THP1 cells overexpressing IL-34 (Molm13-IL-34 and THP1-IL-34), upregulation of the DNA damage-inducible transcript 4 (DDIT4) was detected in both series. Knockdown of DDIT4 effectively inhibited the proliferation, promoted apoptosis and colony formation in Molm13-IL-34 and THP1-IL-34 cells. Our results suggest that DDIT4 mediates the proliferation-promotive effect of IL-34 whereas does not mediate the promotive effect of IL-34 on colony formation in AMoL cells.