Roles of Hematopoietic Stem and Progenitor Cells in Ischemic Cardiovascular Disease.

Macrophage proliferation and skewed myelopoiesis-induced monocytosis, as well as neutrophils, enhance the generation of atherogenic inflammatory cells in a lesion area, leading to plaque formation and Cardiovascular Disease (CVD). Among all risk factors, accumulated data have shown that hyperlipidemia activates Hematopoietic Stem/Progenitor Cells (HSPCs) in the Bone Marrow (BM) niche. Recently, proliferation of Granulocyte-Monocyte Progenitors (GMPs) has been demonstrated to drive skewed myelopoiesis, while HSPCs remain quiescent. In this review, we discuss how HSPCs and GMPs participate in atherosclerosis of mice in terms of proliferation and cell mobilization from BM to peripheral blood and the lesion area. We also describe how the spleen, an extramedullary organ, is involved in skewed myelopoiesis and inflammation in atherosclerosis. We further summarize the clinical evidence of the relationship of HSPCs with coronary stenoses in patients with CVD. Ultimately, this review facilitates understanding the pathological roles of HSPCs and GMPs in atherosclerosis for future treatments.

Atonal bHLH transcription factor 1 is an important factor for maintaining the balance of cell proliferation and differentiation in tumorigenesis.

Establishing the link between cellular processes and oncogenesis may aid the elucidation of targeted and effective therapies against tumor cell proliferation and metastasis. Previous studies have investigated the mechanisms involved in maintaining the balance between cell proliferation, differentiation and migration. There is increased interest in determining the conditions that allow cancer stem cells to differentiate as well as the identification of molecules that may serve as novel drug targets. Furthermore, the study of various genes, including transcription factors, which serve a crucial role in cellular processes, may present a promising direction for future therapy. The present review described the role of the transcription factor atonal bHLH transcription factor 1 (ATOH1) in signaling pathways in tumorigenesis, particularly in cerebellar tumor medulloblastoma and colorectal cancer, where ATOH1 serves as an oncogene or tumor suppressor, respectively. Additionally, the present review summarized the associated therapeutic interventions for these two types of tumors and discussed novel clinical targets and approaches.

Robust target gene discovery through transcriptome perturbations and genome-wide enhancer predictions in Drosophila uncovers a regulatory basis for sensory specification.

A comprehensive systems-level understanding of developmental programs requires the mapping of the underlying gene regulatory networks. While significant progress has been made in mapping a few such networks, almost all gene regulatory networks underlying cell-fate specification remain unknown and their discovery is significantly hampered by the paucity of generalized, in vivo validated tools of target gene and functional enhancer discovery. We combined genetic transcriptome perturbations and comprehensive computational analyses to identify a large cohort of target genes of the proneural and tumor suppressor factor Atonal, which specifies the switch from undifferentiated pluripotent cells to R8 photoreceptor neurons during larval development. Extensive in vivo validations of the predicted targets for the proneural factor Atonal demonstrate a 50% success rate of bona fide targets. Furthermore we show that these enhancers are functionally conserved by cloning orthologous enhancers from Drosophila ananassae and D. virilis in D. melanogaster. Finally, to investigate cis-regulatory cross-talk between Ato and other retinal differentiation transcription factors (TFs), we performed motif analyses and independent target predictions for Eyeless, Senseless, Suppressor of Hairless, Rough, and Glass. Our analyses show that cisTargetX identifies the correct motif from a set of coexpressed genes and accurately predicts target genes of individual TFs. The validated set of novel Ato targets exhibit functional enrichment of signaling molecules and a subset is predicted to be coregulated by other TFs within the retinal gene regulatory network.