Česká Genetická Banka

NATURE: 24. 4. 2014

NATURE: Foxc1 is a critical regulator of haematopoietic stem/progenitor cell niche formation

"Haematopoietic stem and progenitor cells are maintained by special microenvironments known as niches in bone marrow^{1, 2, 3, 4, 5, 6}. Many studies have identified diverse candidate cells that constitute niches for haematopoietic stem cells in the marrow, including osteoblasts^{7, 8, 9, 10}, endothelial cells^{11, 12, 13, 14}, Schwann cells¹⁵, α-smooth muscle actin-expressing macrophages¹⁶ and mesenchymal progenitors such as CXC chemokine ligand (CXCL)12-abundant reticular (CAR) cells^{17, 18}, stem cell factor-expressing cells¹³, nestin-expressing cells¹⁹ and platelet-derived growth factor receptor-α (PDGFR-α)⁺Sca-1⁺CD45⁻Ter119⁻ (PαS) cells²⁰. However, the molecular basis of the formation of the niches remains unclear. Here we find that the transcription factor Foxc1 is preferentially expressed in the adipo-osteogenic progenitor CAR cells essential for haematopoietic stem and progenitor cell maintenance in vivo^{5, 13, 18} in the developing and adult bone marrow. When Foxc1 was deleted in all marrow mesenchymal cells or CAR cells, from embryogenesis onwards, osteoblasts appeared normal, but haematopoietic stem and progenitor cells were markedly reduced and marrow cavities were occupied by adipocytes (yellow adipose marrow) with reduced CAR cells. Inducible deletion of Foxc1 in adult mice depleted haematopoietic stem and progenitor cells and reduced CXCL12 and stem cell factor expression in CAR cells but did not induce a change to yellow marrow. These data suggest a role for Foxc1 in inhibiting adipogenic processes in CAR progenitors. Foxc1 might also promote CAR cell development, upregulating CXCL12 and stem cell factor expression. This study identifies Foxc1 as a specific transcriptional regulator essential for development and maintenance of the mesenchymal niches for haematopoietic stem and progenitor cells."

http://www.nature.com/nature/journal/v508/n7497/full/nature13071.html

 

SCIENCE: High-Resolution Genomic Analysis of Human Mitochondrial RNA Sequence Variation

"Mutations in the mitochondrial genome are associated with multiple diseases and biological processes; however, little is known about the extent of sequence variation in the mitochondrial transcriptome. By ultra-deeply sequencing mitochondrial RNA (>6000×) from the whole blood of ~1000 individuals from the CARTaGENE project, we identified remarkable levels of sequence variation within and across individuals, as well as sites that show consistent patterns of posttranscriptional modification. Using a genome-wide association study, we find that posttranscriptional modification of functionally important sites in mitochondrial transfer RNAs (tRNAs) is under strong genetic control, largely driven by a missense mutation in MRPP3 that explains ~22% of the variance. These results reveal a major nuclear genetic determinant of posttranscriptional modification in mitochondria and suggest that tRNA posttranscriptional modification may affect cellular energy production."

http://www.sciencemag.org/content/344/6182/413.abstract