Inflammation Regulates Haematopoietic Stem Cells and Their Niche

Round 1

Reviewer 1 Report

Thank you for providing an opportunity to review the manuscript titled “Inflammation regulates haematopoietic stem cells and their niche” by Nicole Pui-Yu Ho and Hitoshi Takizawa. 

In this review article, the authors recapitulates the current knowledge about how acute, prolonged or pathological inflammatory conditions impact on HSC functions.

The authors have explained very well how the different inflammatory conditions modulates HSC microenvironment and modulates its function towards expansion, differentiation or senescence. They have also mentioned by modulating the certain cytokines such as G-CSF can mobilize HSC from BM to blood stream and activates extra medullary hematopoiesis, which they point out have clinical implications. 

In addition, the authors have also mentioned how acute, chronic or pathological inflammatory signals reprograms the HSC and HSC niche metabolic profile from an anaerobic glycolysis to oxidative phoshorylation, which increases ROS production and eventually dimities HSC function. The implications of  chronic inflammation s such as obesity, atherosclerosis, autoimmune conditions and malignancies on HSC functions have also been discussed very well.

The manuscript also details the role of HSC niche in maintaining homeostasis and how inflammation contributes changes in the niche, which intern directs HSC cells to respond.

Altogether the authors have written the manuscript very well and I recommend the manuscript for the publication in its current from. 

Reviewer 2 Report

In the present manuscript titled Inflammation regulates haematopoietic stem cells and their niche,  authors systematically summarized the various  factors, disease conditions that leads to inflammation dependent regulation of  HSC and their niche. The present manuscript also provides insights in to future challenges and directions for HSC regulation by inflammation.