N-Cadherin Expression Level Distinguishes Reserved versus Primed States of Hematopoietic Stem Cells

SummaryOsteoblasts expressing the homophilic adhesion molecule N-cadherin form a hematopoietic stem cell (HSC) niche. Therefore, we examined how N-cadherin expression in HSCs relates to their function. We found that bone marrow (BM) cells highly expressing N-cadherin (N-cadherinhi) are not stem cells, being largely devoid of a Lineage−Sca1+cKit+ population and unable to reconstitute hematopoietic lineages in irradiated recipient mice. Instead, long-term HSCs form distinct populations expressing N-cadherin at intermediate (N-cadherinint) or low (N-cadherinlo) levels. The minority N-cadherinlo population can robustly reconstitute the hematopoietic system, express genes that may prime them to mobilize, and predominate among HSCs mobilized from BM to spleen. The larger N-cadherinint population performs poorly in reconstitution assays when freshly isolated but improves in response to overnight in vitro culture. Their expression profile and lower cell-cycle entry rate suggest N-cadherinint cells are being held in reserve. Thus, differential N-cadherin expression reflects functional distinctions between two HSC subpopulations

Additional file 1: Figure S1. of Improved transcription and translation with L-leucine stimulation of mTORC1 in Roberts syndrome

Quantitation of Western blotting in Fig. 1a and b. Figure S2. Gene transcription and translation pattern of WT cells and ESCO2-Corrected cells. Figure S3. The boxplots display the show expression of mRNAs with 5’TOP sequences (a), PRTE sequences (b), and Babel genes (c). Figure S4. Motif and GO terms associated with genes with increased translational efficiency upon L-leucine treatment in RBS cells. Figure S5. mTORC2 show regulated genes do not show a coherent response to L-leucine. Figure S6. GTL2-regulated miRNAs are increased in RBS cells independent of L-Leu. Figure S7. Homeobox (HOX) gene expression is reduced in RBS cells. (ZIP 4.64 MB

A Complex Oscillating Network of Signaling Genes Underlies the Mouse Segmentation Clock

A Complex Oscillating Network of Signaling Genes Underlies the Mouse Segmentation Cloc

Poised RNA Polymerase II Changes over Developmental Time and Prepares Genes for Future Expression

Poised RNA polymerase II (Pol II) is predominantly found at developmental control genes and is thought to allow their rapid and synchronous induction in response to extracellular signals. How the recruitment of poised RNA Pol II is regulated during development is not known. By isolating muscle tissue from Drosophila embryos at five stages of differentiation, we show that the recruitment of poised Pol II occurs at many genes de novo and this makes them permissive for future gene expression. A comparison with other tissues shows that these changes are stage specific and not tissue specific. In contrast, Polycomb group repression is tissue specific, and in combination with Pol II (the balanced state) marks genes with highly dynamic expression. This suggests that poised Pol II is temporally regulated and is held in check in a tissue-specific fashion. We compare our data with findings in mammalian embryonic stem cells and discuss a framework for predicting developmental programs on the basis of the chromatin state