A chromatin perspective on metabolic and genotoxic impacts on hematopoietic stem and progenitor cells

Abstract

The fate determination in self-renewal and differentiation of hematopoietic stem and progenitor cells (HSCs and HPCs) is ultimately controlled by gene expression, which is profoundly influenced by the global and local chromatin state. Cellular metabolism directly influences the chromatin state through the dynamic regulation of the enzymatic activities that modify DNA and histones, but also generates genotoxic metabolites that can damage DNA and thus pose threat to the genome integrity. On the other hand, mechanisms modulating the chromatin state impact metabolism by regulating the expression and activities of key metabolic enzymes. Moreover, through regulating either DNA damage response directly or expression of genes involved in this process, chromatin modulators play active and crucial roles in guarding the genome integrity, breaching of which result in defective HSPC function. Therefore, HSPC function is regulated by the dynamic and two-way interactions between metabolism and chromatin. Here, we review recent advances that provide a chromatin perspective on the major impacts the metabolic and genotoxic factors can have on HSPC function and fate determination.

Hematopoietic stem cells are a reservoir for trained immunity in autoimmune disease

“…These data suggest that glycolytic activity is clearly coupled to the establishment of immune training, as evaluated in short-term assays using BMDMs or PBMCs (Bekkering et al ., 2016, 2018; Arts et al ., 2016). On the other hand, once the epigenetic program for immune training is established, glycolysis may become dispensable either as a source of energy for induction of inflammatory gene programs and/or as a source for catabolic derivatives used for epigenetic modifications, like acetyl-CoA and/or TCA cycle intermediates that tune the activity of epigenetic writers and/or erasers (Fawal and Davy, 2018; Domínguez-Andrés et al ., 2019; Yang and Jiang, 2020). Hence, trained myeloid cells derived from these HSC may either come to rely on other sources of energy (amino/fatty acids, autophagy) for enhanced inflammatory and immune function.…”

Protocol to produce high-titer retrovirus for transduction of mouse bone marrow cells

“…We usually obtain 40–60 × 10 6 mononuclear bone marrow cells from each 8–12 weeks old mouse by following the protocol as mentioned above and else ( Yang et al., 2019 ; Yang and Jiang, 2020 ). 5-FU is a nucleotide analogue that is incorporated into DNA during the S-phase of the cell cycle.…”