Project description:Activation of mostly quiescent hematopoietic stem cells (HSC) is a prerequisite for life-long blood production1, 2. This process requires major molecular adaptations to meet the regulatory and metabolic requirements for cell division3-8. The mechanisms governing cellular reprograming upon stem cell activation and their subsequent return to quiescence are still not fully characterized. Here, we describe a role for chaperone-mediated autophagy (CMA)9, a selective form of lysosomal protein degradation, in sustaining adult HSC function. CMA is required for stem cell protein quality control and upregulation of fatty acid metabolism upon HSC activation. We identify that CMA activity decreases with age in HSC and show that genetic or pharmacological activation of CMA can restore functionality of old HSC. Together, our findings provide mechanistic insights into a new role for CMA in sustaining quality control, appropriate energetics and overall long-term hematopoietic stem cell function. Our work supports that CMA may be a promising therapeutic target to enhance hematopoietic stem cell function in conditions such as aging or stem cell transplantation.

2021-03-05 | PXD022196 | Pride

Long Non-coding RNAs Control Hematopoietic Stem Cell (HSC) Function (ChIRP-seq)

Project description:Long non-coding RNAs (lncRNAs) have recently emerged as new players in gene expression regulation. Whether and how lncRNAs might control hematopoietic stem cell (HSC) function remains largely unknown. Here, we profiled the transcriptome of purified long-term HSCs by deep RNA-sequencing and identified thousands of un-annotated transcripts of which 323 are predicted to be lncRNAs. Comparison of their expression in differentiated lineages represented by B cells (B220+) and Granulocytes (Gr1+), revealed that 159 are likely to be HSC-specific. Knockdown of two such non-coding genes (LincHSC-1 and LincHSC-2) indicated that they regulate HSC lineage differentiation, possibly via targeting cell cycle regulators and chromatin modification enzymes. Taken together, we comprehensively identify lncRNAs in HSC and show to examples that play important roles in HSC function.

2015-03-13 | GSE66819 | GEO

Long Non-coding RNAs Control Hematopoietic Stem Cell (HSC) Function (RNA-Seq)

Project description:Long non-coding RNAs (lncRNAs) have recently emerged as new players in gene expression regulation. Whether and how lncRNAs might control hematopoietic stem cell (HSC) function remains largely unknown. Here, we profiled the transcriptome of purified long-term HSCs by deep RNA-sequencing and identified thousands of un-annotated transcripts of which 323 are predicted to be lncRNAs. Comparison of their expression in differentiated lineages represented by B cells (B220+) and Granulocytes (Gr1+), revealed that 159 are likely to be HSC-specific. Knockdown of two such non-coding genes (LncHSC-2 and LncHSC-1) indicated that they regulate HSC lineage differentiation, possibly via targeting cell cycle regulators and chromatin modification enzymes. Taken together, we comprehensively identify lncRNAs in HSC and show to examples that play important roles in HSC function.

2014-12-30 | GSE53928 | GEO

Long Non-coding RNAs Control Hematopoietic Stem Cell (HSC) Function (ChIP-Seq)

2014-12-30 | GSE63276 | GEO

Microarray from both control and activated Hematopoietic stem cells

Project description:Activation of mostly quiescent hematopoietic stem cells (HSC) is a prerequisite for life-long blood production. This process requires major molecular adaptations to meet the regulatory and metabolic requirements for cell division. The mechanisms governing cellular reprograming upon stem cell activation and their subsequent return to quiescence are still not fully characterized. Here, we describe a central role for a selective type of autophagy (CMA) in sustaining adult HSC function both through to stem cell protein quality control and to timely stimulation of linoleic fatty acid metabolism upon HSC activation. We identify that reduced CMA in old HSC contributes to the loss of stem cell activity during aging and show that genetic or chemical activation of CMA can restore old HSC function. Together, our findings provide mechanistic insights into a new role for CMA in sustaining long-term HSC quality control, appropriate energetics and overall hematopoietic stem cell function. Our work supports that CMA may be a promising therapeutic target to enhance hematopoietic stem cell function in conditions such as aging or stem cell transplantation. We used microarrays to identify the most affected genes and pathways by CMA deficiency in both basal and activated conditions.

2020-10-23 | GSE142632 | GEO

Single-cell dissection of long non-coding RNAs pivotal for embryonic hematopoietic stem cell development

Project description:Single-cell dissection of long non-coding RNAs pivotal for embryonic hematopoietic stem cell development

| PRJNA428181 | ENA