Towards an integrated understanding of inflammatory pathway influence on hematopoietic stem and progenitor cell differentiation

• Published in: BioEssays Vol. 46; no. 4; pp. e2300142 - n/a
• Main Authors: Allara, Michael, Girard, Juliet R.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2024
• Subjects: Cell differentiation; Cells (biology); Differentiation (biology); Hematopoiesis; hematopoietic stem and progenitor cells; Hematopoietic stem cells; Hemopoiesis; In vivo methods and tests; infection; Inflammation; injury; microbiota; Pattern recognition; Pattern recognition receptors; Phenotypes; Progenitor cells; Receptors; Signal transduction; stem cell niche; Transplantation; microbiota; pattern recognition receptors; hematopoiesis; infection; stem cell niche; hematopoietic stem and progenitor cells; injury
• ISSN: 0265-9247; 1521-1878
• DOI: 10.1002/bies.202300142

Recent research highlights that inflammatory signaling pathways such as pattern recognition receptor (PRR) signaling and inflammatory cytokine signaling play an important role in both on‐demand hematopoiesis as well as steady‐state hematopoiesis. Knockout studies have demonstrated the necessity of several distinct pathways in these processes, but often lack information about the contribution of specific cell types to the phenotypes in question. Transplantation studies have increased the resolution to the level of specific cell types by testing the necessity of inflammatory pathways specifically in donor hematopoietic stem and progenitor cells (HSPCs) or in recipient niche cells. Here, we argue that for an integrated understanding of how these processes occur in vivo and to inform the development of therapies that modulate hematopoietic responses, we need studies that knockout inflammatory signaling receptors in a cell‐specific manner and compare the phenotypes caused by knockout in individual niche cells versus HSPCs. Hematopoiesis is influenced by inflammatory pathways downstream of several inputs including infection, injury, healthy microbiota, and developmental signals. These inputs may be sensed directly by hematopoietic stem and progenitor cells (HSPCs) or indirectly through HSPC niche cells. This article explores recent advances in understanding which cells contribute to these mechanisms.