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Congenital Central Hypoventilation Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Expressed during neural development in the nuclei of brainstem areas that contain pathways controlling breathing and auditory functions [5], PHOX2B is regulated transcriptionally by itself, as well as E2a and Hand2 at specific sympathetic and enteric nervous system developmental stages. Other proteins that may play a possible role in the regulation of PHOX2B are SOX10, PHOX2A, and HASH1. Further, by forming trimer with Pbx1 and Meis1, Hoxb1 and Hoxb2 also contribute to the regulation of PHOX2B transcription.
ENTRIES A–Z
Published in Philip Winn, Dictionary of Biological Psychology, 2003
A GENE family, in which the genes contain a homeobox, a highly conserved sequence of DNA that codes for a protein of approximately 60 AMINO ACIDS, known as a homeodomain protein. These proteins are transcription factors, and are expressed in spatially and temporally distinct patterns in different tissues of an organism during DEVELOPMENT. Studies of GENE KNOCKOUT and MUTATION of these genes indicate that they are important in determining the position and morphological fate of the cells in which they are found. For example, knockout of Hoxa-1, one of the box family of homeobox genes, causes delay in closure of the NEURAL TUBE at the level of the HINDBRAIN, and improper position of CRANIAL NERVES, resulting in death of the organism shortly after birth. Knockout of another box gene, Hoxb-1, results in failure of migration of MOTOR NEURONS to their proper positions, suggesting that this gene is involved in path-finding of motor neurons to their skeletal targets.
Artificial gametes The oocyte
Published in David K. Gardner, Ariel Weissman, Colin M. Howles, Zeev Shoham, Textbook of Assisted Reproductive Techniques, 2017
Evelyn E. Telfer, Kelsey M. Grieve
The identification of early germ cells within culture demonstrates recapitulation of the earliest stages of the complex pathway for germ cell development; however, prior to germ cell migration, germ cell fate is induced in the epiblast cells in mice by bone morphogenetic protein 4 (BMP4) signaling from the surrounding soma (6). Epiblast-like cells (EpiLCs) have been induced from mESCs with gene expression consistent with pre-gastrulating epiblasts. BMP4 induced expression of Blimp1 in EpiLCs and further gene expression analysis also showed up-regulation of Nanos3, Dppa3 and Prdm14 associated with primordial germ cell specification and down-regulation of somatic markers Hoxa1, Hoxb1, and Snai1—these observations were seen in conjunction with epigenetic changes (7), replicating in vivo differentiation of epiblast cells into primordial germ cells. These results suggest successful differentiation of EpiLCs to primordial germ cell-like cells (PGCLCs) in vitro in a similar fashion to the in vivo situation. BMP4-dependent differentiation of PGCLCs could be inhibited by Noggin (a BMP4 antagonist), whereas Wnt3a—another mesoderm-promoting factor—also induced PGCLCs in culture (8), illustrating the importance of somatic factors in in vitro differentiation of germ cells. PGCLCs derived from embryoid bodies (EBs) differentiated into oocyte-like cells with expression of oocyte-specific genes (Figa, GDF9, ZP1, ZP2, and ZP3) and an early meiotic marker (SCP3) when co-cultured with granulosa cells (9); similar results were observed when PGCLCs were co-cultured with Chinese hamster ovary cells (10). However, these results could not be replicated with granulosa cell-conditioned medium (9), suggesting an important role for cell-cell interactions with ovarian somatic cells. Using a reconstituted ovary model, PGCLCs combined with embryonic ovarian somatic cells and xeno-transplanted to the ovarian bursa of immune-deficient recipient mice generated oocyte-like cells within developing follicles (Figure 30.2).
Hsa-circ_0003420 induces apoptosis in acute myeloid leukemia stem cells and impairs stem cell properties
Published in Immunopharmacology and Immunotoxicology, 2021
Guoqiang Lin, Yingying Fei, Yanming Zhang
circRNAs expressed in hematopoietic cells are thought to regulate the physiological and pathological characteristics of the cell population derived from HSCs. A previous study reported that circRNAs are differentially expressed in acute lymphoblastic leukemia (ALL) and suggested that in primitive B cells (CD19+) and HSCs (CD34+), more than 10% of the transcripts encoded by numerous genes are circular [21]. For example, circ-BACH1 (exons 2–4) is expressed in HSCs [22]. However, the differential expression of circRNAs in LSCs has been rarely reported. Here, we found that hsa-circ_0003420 is lowly expressed in AML patients with poor prognosis and different AML cell lines. The upregulation of hsa-circ_0003420 impaired xenograft tumorigenesis in mice. Furthermore, hsa-circ_0003420 attenuated cell replication and viability, induced apoptosis, and abated the LSC phenotype of KG-1a cells. In addition, bioinformatics and DLRA analyses revealed that hsa-circ_0003420 negatively regulates the expression of IGF2BP1 by targeting its 3′-UTR, thereby influencing the expression of ALDHA1A1, HOXB1, and MYB downstream of IFG2BP1.
All-Trans Retinoic Acid Rescues the Tumor Suppressive Role of RAR-β by Inhibiting LncHOXA10 Expression in Gastric Tumorigenesis
Published in Nutrition and Cancer, 2021
Chen Wang, Didi Zhao, Kexin Wang, Lei Gao, Yue He, Hanhan Wu, Liang Ruan, Wenjun Chen, Daoming Zhang, Tao Xia, Shiqing Qian, Zhining Liu, Yi Yang, Wanshui Yang, Anla Hu, Qihong Zhao
Despite their lack of protein coding capacity, LncRNAs are functional molecules. Numerous studies have shown that LncRNAs can interact with chromatin-modifying complexes as well as modify the conformation of nuclear domains and the activity of transcriptional enhancers (37–40). Furthermore, LncRNAs also regulate modifications at the post-transcriptional level, such as the regulation of mRNA decay, protein translation, and splicing (41). It was reported that there is a RARE sequence located in the enhancer of HOXA10 (22), suggesting that it may respond to ATRA signaling. In the classical model of ATRA-dependent gene regulation, ATRA binds to the RAR/RXR heterodimers that bind the RARE sequences of targeted gene to activate transcription of the gene (42,43). In this context, the RARE sequence could be seen as a cis-element. However, there are also some exceptions to the classical models. For instance, RARE sequences of fibroblast growth factor 8 (Fgf8) and homeobox B1 (HOXB1) regulate gene repression rather than activation, where ATRA can recruit PRC2 and HDAC and trigger H3K27me3 when binding to RARE sequences (44,45). However, whether the RARE sequence in the enhancer of HOXA10 promotes or represses gene transcription was unclear. Therefore, we treated GES-1 cells with different concentrations of ATRA for 24 h, and qRT-PCR results showed that the expression level of LncHOXA10 was significantly inhibited by ATRA in a dose-dependent manner. Meanwhile, RAR-β, regarded as tumor suppressor in many tumors, also contains a RARE sequence and positively responds to ATRA signaling. The qRT-PCR and Western blot results revealed that ATRA could induce RAR-β expression at both the transcriptional and translational levels, leading us to hypothesis that LncHOXA10 may competitively bind to the RARE sequence located in the RAR-β enhancer and keep RAR-β away from ATRA signaling. Therefore, we selectively silenced and overexpressed LncHOXA10 in GES-1 cells. The qRT-PCR and Western blot assay results indicated that LncHOXA10 negatively regulates RAR-β expression at both the transcriptional and translational levels, supporting our hypothesis. Subsequently, we treated LncHOXA10-overexpressing GES-1 cells with 5 μM ATRA and observed that LncHOXA10 was significantly suppressed and that of RAR-β markedly increased at both the mRNA and protein levels. Consistent with these results, we observed that ATRA could inhibit in vitro malignant tumor cell growth and motility induced by LncHOXA10.