Volume 03 · Issue 01 · 2021

Hematopoietic stem cells (HSCs) replenish all lineages of blood cells throughout the lifespan. During aging, the repopulation capacity of HSCs declined, and aged HSCs display a tendency for myeloid differentiation. Several intrinsic and extrinsic factors have been identified to promote HSCs aging. In this review, we focus on the contribution of aging-associated inflammation in provoking HSCs aging and discuss the future research direction of inflammation and HSC aging.

Tcf12 has been identified as one of the main helix-loop-helix transcription factors that regulates T cell development from double negative to double positive stage transition. While, the function of Tcf12 in hematopoietic stem cells remains not investigated. In this study, we observed that Tcf12 is expressed in HSCs and targeted deletion of Tcf12 in hematopoietic cells results in increased frequency and absolute number of HSCs, but compromises the reconstitution capacity of HSCs. Further analysis reveals that Tcf12 is dispensable for the self-renewal of HSCs. The declined reconstituted capacity of Tcf12^-/- HSCs stems from the decrease in the ability to differentiate into lymphoid-primed multipotent progenitors, and furthermore B and T lineages.

Next-generation sequencing technology has been widely utilized for the diagnosis of Fanconi anemia (FA). However, mixed cell sequencing and chimerism of FA patients may lead to unconfirmed genetic subtypes. Herein, we introduced two novel diagnostic methods, including single-cell sequencing and capillary nano-immunoassay. One FA case with FANCM c.4931G>A p.R1644Q and FANCD1 c.6325G>A p.V2109I was studied. The DNA of 28 cells was amplified and eight types of cells were observed after Sanger sequencing. There were two homozygous mutations (FANCM/FANCD1). Furthermore, the capillary nano-immunoassay was conducted to analyze the expression profile of FA-associated proteins. Abnormal FANCM and FANCD1 expressions simultaneously existed. This case was thus diagnosed as FA-D1/FA-M dual subtype. Compared with mixed cell sequencing, single-cell sequencing data shows more accuracy for the FA subtype evaluation, while the capillary nano-immunoassay is a good method to detect the expression profile of abnormal or modified FA protein.

To understand the behavior and function of bone-marrow mesenchymal cells (BMMCs), we overviewed the morphological presentation of BMMCs in bone-marrow granules (b-BMMCs), isolated BMMCs (i-BMMCs), and BMMCs (c-BMMCs) cultured in H4434 methylcellulose semisolid and MEM media. All samples were derived from bone-marrow aspirates of 30 patients with hematocytopenia. Light microscopy exhibited b-BMMCs and i-BMMCs characterized by abundant cytoplasm and irregular shape in bone-marrow smears, as well as c-BMMCs in culture conditions. Scanning electron microscopy demonstrated cultured c-BMMCs with a sheet-like feature enveloping hematopoietic cells. Transmission electron microscopy revealed b-BMMCs constructing a honeycomb-like structure by thin bifurcate processes among hematopoietic cells. Furthermore, i-BMMCs had bifurcate parapodiums on the surface and prominent rough endoplasmic reticulum (rER) connected with the plasmalemma of the parapodiums. The detailed images suggested that rER may serve as a membrane resource for plasmalemmal expansion in BMMCs in bone marrow.