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Transcriptome study for early hematopoiesis--achievement, challenge and new opportunity.

ABSTRACT: Hematopoietic stem progenitor cells are the source for the entire hematopoietic system. Studying gene expression in hematopoietic stem progenitor cells will provide information to understand the genetic programs controlling early hematopoiesis, and to identify the gene targets to interfere hematopoietic disorders. Extensive efforts using cell biology, molecular biology, and genomics approaches have generated rich knowledge for the genes and functional pathways involving in early hematopoiesis. Challenges remain, however, including the rarity of the hematopoietic stem progenitor cells that set physical limitation for the study, the difficulty for reaching comprehensive transcriptome detection under the conventional genomics technologies, and the difficulty for using conventional biological methods to identify the key genes among large number of expressed genes controlling stem cell self-renewal and differentiation. The newly developed single-cell transcriptome method and the next-generation DNA sequencing technology provide new opportunities for transcriptome study for early hematopoietic. Using systems biology approach may reveal the insight of the genetic mechanisms controlling early hematopoiesis.

SUBMITTER: Wang SM

PROVIDER: S-EPMC2875260 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Transcriptome study for early hematopoiesis--achievement, challenge and new opportunity.

Wang San Ming SM Zhang Michael Q MQ

Journal of cellular physiology 20100601 3

Hematopoietic stem progenitor cells are the source for the entire hematopoietic system. Studying gene expression in hematopoietic stem progenitor cells will provide information to understand the genetic programs controlling early hematopoiesis, and to identify the gene targets to interfere hematopoietic disorders. Extensive efforts using cell biology, molecular biology, and genomics approaches have generated rich knowledge for the genes and functional pathways involving in early hematopoiesis. C ...[more]

PMID: 20143329

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Project description:It is now recognized that the immune system can be a key component of restraint and control during the neoplastic process. Human papillomavirus (HPV)-associated cancers of the anogenital tract and oropharynx represent a significant clinical problem but there is a clear opportunity for immune targeting of the viral oncogene expression that drives cancer development. However, high-risk HPV infection of the target epithelium and the expression of the E6/E7 oncogenes can lead to early compromise of the innate immune system (loss of antigen-presenting cells) facilitating viral persistence and increased risk of cancer. In these circumstances, a succession of interacting and self-reinforcing events mediated through modulation of different immune receptors, chemokine and cytokine responses (CCL20; CCL2; CCR2; IL-6; CCR7; IL-12) further promote the generation of an immune suppressive microenvironment [increased levels of Tregs, Th17, myeloid-derived suppressor cells (MDSCs) and PD-L1]. The overexpression of E6/E7 expression also compromises the ability to repair cellular DNA, leading to genomic instability, with the acquisition of genetic changes providing for the selection of advantaged cancer cells including additional strategies for immune escape. Therapeutic vaccines targeting the HPV oncogenes have shown some encouraging success in some recent early-phase clinical trials tested in patients with HPV-associated high-grade anogenital lesions. A significant hurdle to success in more advanced disease will be the local and systemic immune suppressive factors. Interventions targeting the different immunosuppressive components can provide opportunity to release existing or generate new and effective antitumour immunity. Treatments that alter the protumour inflammatory environment including toll-like receptor stimulation, inhibition of IL-6-related pathways, immune-checkpoint inhibition, direct modulation of MDSCs, Tregs and macrophages could all be useful in combination with therapeutic HPV vaccination. Future progress in delivering successful immunotherapy will depend on the configuration of treatment protocols in an insightful and timely combination.

Dataset Information

Transcriptome study for early hematopoiesis--achievement, challenge and new opportunity.

Publications

Transcriptome study for early hematopoiesis--achievement, challenge and new opportunity.

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