Linker Histone Regulates The Myeloid Versus Lymphoid Bifurcation Of Multipotent Hematopoietic Stem And Progenitors
Our bodies contain special “master” cells called multipotent hematopoietic stem and progenitor cells (HSPCs) that have the amazing ability to develop into all different types of blood cells. These include myeloid cells, which are part of our immediate immune response (like fighting bacteria), and lymphoid cells, which are responsible for more specific and long-term immunity (like T and B cells that remember past infections). The decision of an HSPC to become a myeloid or lymphoid cell is a critical “bifurcation” or branching point.
Historically, the exact mechanisms controlling this fundamental decision have been unclear. This research sheds light on a key player: linker histones, which are proteins that act like spools, helping to organize and compact our DNA within cells. When these linker histones increase, they make certain parts of the DNA less accessible. Specifically, a type of linker histone called H1.0 was found to promote the development of lymphoid cells. It does this by making the DNA regions associated with myeloid-driving genes less available, effectively “turning down” the instructions for becoming myeloid cells.
This discovery is significant because an imbalance favoring myeloid cells, known as myeloid bias, often occurs with aging or in certain diseases like inflammation and cancer. Understanding how linker histones influence this balance provides new avenues for potential treatments. By finding ways to maintain or increase the levels of specific linker histones, or to block the enzymes that break them down, we might be able to guide these master cells towards a more balanced production of immune cells, potentially counteracting age-related immune decline or disease progression.
Source: link to paper