40.5: Multipotency of Hematopoietic Stem Cells

The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term renewal capacity.

The long-term HSCs rarely divide as they maintain long gaps between successive cell divisions while keeping their metabolic activity to the bare minimum. Thus, the LTRCs undergo a few rounds of symmetric cell divisions before entering the state of dormancy. This allows them to expand the number of HSCs and maintain a stem cell pool before exhausting their regenerative and self-renewal potential.

LTRCs produce the more active multipotent short-term repopulating cells (STRC) in response to external stimuli. STRCs undergo fewer self-renewal divisions than the LTRCs and differentiate into specific blood or immune cells. LTRCs and STRCs find application in engraftment and therapeutic studies. The LTRCs can sustain hematopoiesis for upto four months upon transplantation into the recipients, while transplantation of STRCs supports hematopoiesis for only a few weeks. A delicate balance between dormancy and differentiation stimuli maintains the HSC population for the long run. A slow or non-responsive quiescent HSCs leave the body devoid of differentiated blood cells such as erythrocytes, phagocytes, and lymphocytes which are necessary for transporting nutrients or providing immune surveillance. In contrast, highly active HSCs exhaust the stem cell population making them unavailable to renew, repair, or replace blood cells lost due to an injury or infection.

Hematopoietic stem cells  or HSCs are multipotent, meaning they can form all types of blood cells.

In an embryo, hematopoiesis occurs in the liver, where an HSC divides symmetrically, producing two daughter cells. These HSCs continue to multiply by self-renewal.

Under the influence of growth factors called cytokines, the HSCs differentiate into progenitors of blood cells.

In adults, HSCs reside in the bone marrow and interact with the surrounding stromal cells .

Receptor-ligand interaction brings the HSC and the stromal cells together.  Such cell-cell contact inhibits HSC proliferation as they enter the G₀ state of the cell cycle and become non-dividing or quiescent.

Upon tissue injury, vascular endothelium releases growth factors that allow the quiescent HSCs to lose contact with the surrounding stroma and migrate to the blood vessels.

HSCs now undergo asymmetric division, maintaining the HSC pool and forming committed progenitors that differentiate into mature blood cells.