Technical Advances in Single-Cell RNA Sequencing and Applications in Normal and Malignant Hematopoiesis

Abstract

Single-cell RNA sequencing (scRNA-seq) has been tremendously developed in the past decade owing to overcoming challenges associated with isolation of massive quantities of single cells. Previously, cell heterogeneity and low quantities of available biological material posed significant difficulties to scRNA-seq. Cell-to-cell variation and heterogeneity are fundamental and intrinsic characteristics of normal and malignant hematopoietic cells; this heterogeneity has often been ignored in omics studies. The application of scRNA-seq has profoundly changed our comprehension of many biological phenomena, including organ development and carcinogenesis. Hematopoiesis, is actually a maturation process for more than ten distinct blood and immune cells, and is thought to be critically involved in hematological homeostasis and in sustaining the physiological functions. However, aberrant hematopoiesis directly leads to hematological malignancy, and a deeper understanding of malignant hematopoiesis will provide deeper insights into diagnosis and prognosis for patients with hematological malignancies. Here, we aim to review the recent technical progress and future prospects for scRNA-seq, as applied in physiological and malignant hematopoiesis, in efforts to further understand the hematopoietic hierarchy and to illuminate personalized therapy and precision medicine approaches used in the clinical treatment of hematological malignancies.

Tuning TPO-R signaling to influence hematopoietic stem cell differentiation and inhibit essential thrombocythemia

“…TPO-DBs are able to deliver customized intensities of downstream TPO-R signals, and thus mimic the physiological conditions of the TPO regulation while more tightly controlling downstream signaling output. In addition, the TPO DBs split the functions of TPO with regard to megakaryopoiesis and HSC expansion, a unique feature, retained at least short-term stem-cell-like properties; thus, these culture conditions appear optimal for stem-cell maintenance.Using single-cell transcriptomics (scRNA-seq) in conjunction with protein expression studies, we confirmed that the stem cells generated by DBs (which we found partially block the activity of MPL) produce an original pool of stem cells in vitro(38,39). By clustering HSC and MPP we can conclude that after nearly two weeks of culture, the HSCAK111 populations are closer to HSC than MPP populations.…”

Tuning MPL signaling to influence hematopoietic stem cell differentiation and inhibit essential thrombocythemia progenitors

“…Using single-cell transcriptomics (scRNA-seq) in conjunction with protein expression studies, we confirmed that the stem cells generated by DBs produce an original pool of stem cells in vitro ( 45 , 46 ). By clustering HSPCs and MPPs we can conclude that after nearly 2 wk of culture, the HSC AK111 populations are closer to HSPC than MPP populations.…”

Single-Cell RNA Sequencing Analysis Reveals Greater Epithelial Ridge Cells Degeneration During Postnatal Development of Cochlea in Rats

“…In the present work, we revealed the changes of GER cells profiles by single-cell RNA sequencing technology (Baslan et al, 2012;Shapiro et al, 2013;Huang et al, 2018). We also observed the change of the expression and regulation of key genes and signaling pathways enriched biological processes in these clusters during cochlear development.…”