Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sensory receptors for hearing and balance are the hair cells of the cochlea and vestibular organs of the inner ear. Permanent hearing and balance deficits can be triggered by genetic susceptibilities or environmental factors such as infection. Unlike mammalian hair cells that have a limited capacity for regeneration, the vestibular organ of the avian ear is constantly undergoing hair cell regeneration, whereas the avian cochlea undergoes regeneration only when hair cells are damaged. In order to gain insights into the genetic programs that govern the regenerative capacity of hair cells, we interrogated custom human cDNA microarrays with sensory epithelial cell targets from avian inner ears. The arrays contained probes from conserved regions of approximately 400 genes expressed primarily in the inner ear and approximately 1500 transcription factors (TF). Highly significant differences were observed for 20 inner-ear genes and more than 80 TFs. Genes up-regulated in the cochlea included BMP4, GATA3, GSN, FOXF1 and PRDM7. Genes up-regulated in the utricle included SMAD2, KIT, beta-AMYLOID, LOC51637, HMG20B and CRIP2. Many of the highly significant changes were validated by Q-PCR and in situ methods. Some of the observed changes implicated a number of known biochemical pathways including the c-kit pathway previously observed in melanogenesis. Twenty differentially expressed TFs map to chromosomal regions harboring uncloned human deafness loci, and represent novel candidates for hearing loss. The approach described here also illustrates the power of utilizing conserved human cDNA probes for cross-species comparisons.
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PMID:Gene expression differences in quiescent versus regenerating hair cells of avian sensory epithelia: implications for human hearing and balance disorders. 1276 Oct 41

Rationale: Disruption of alveologenesis is associated with severe pediatric lung disorders, including bronchopulmonary dysplasia (BPD). Although c-KIT+ endothelial cell (EC) progenitors are abundant in embryonic and neonatal lungs, their role in alveolar septation and the therapeutic potential of these cells remain unknown.Objectives: To determine whether c-KIT+ EC progenitors stimulate alveologenesis in the neonatal lung.Methods: We used single-cell RNA sequencing of neonatal human and mouse lung tissues, immunostaining, and FACS analysis to identify transcriptional and signaling networks shared by human and mouse pulmonary c-KIT+ EC progenitors. A mouse model of perinatal hyperoxia-induced lung injury was used to identify molecular mechanisms that are critical for the survival, proliferation, and engraftment of c-KIT+ EC progenitors in the neonatal lung.Measurements and Main Results: Pulmonary c-KIT+ EC progenitors expressing PECAM-1, CD34, VE-Cadherin, FLK1, and TIE2 lacked mature arterial, venal, and lymphatic cell-surface markers. The transcriptomic signature of c-KIT+ ECs was conserved in mouse and human lungs and enriched in FOXF1-regulated transcriptional targets. Expression of FOXF1 and c-KIT was decreased in the lungs of infants with BPD. In the mouse, neonatal hyperoxia decreased the number of c-KIT+ EC progenitors. Haploinsufficiency or endothelial-specific deletion of Foxf1 in mice increased apoptosis and decreased proliferation of c-KIT+ ECs. Inactivation of either Foxf1 or c-Kit caused alveolar simplification. Adoptive transfer of c-KIT+ ECs into the neonatal circulation increased lung angiogenesis and prevented alveolar simplification in neonatal mice exposed to hyperoxia.Conclusions: Cell therapy involving c-KIT+ EC progenitors can be beneficial for the treatment of BPD.
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PMID:Postnatal Alveologenesis Depends on FOXF1 Signaling in c-KIT+ Endothelial Progenitor Cells. 3134 12