Research Summary

Understanding the role of Periostin-Itgav interactions in adult and fetal hematopoiesis

The pool of hematopoietic stem cells (HSCs) required to keep up the production of all the blood cells in specific proportion is generated during fetal development. Multiple transient sites of hematopoiesis appear during development (See figure below) and this highly dynamic developmental process ends in establishing marrow of the freshly developing bones as the final site where blood cells will be produced for the rest of the life. Every stage of the life of an HSC, at least in part, is governed by extrinsic signals, which can come from immediate neighboring cells or a variety of humoral/chemical/physical factors (See figure below). Alteration in the dynamics of these factors results in age related deterioration of stem cell potential leading to poor tissue function. HSCs happen to be one of the most studied of all the stem cells and are widely used in clinics for the treatment of a variety of hematologic and non-hematologic ailments. Evidently, expansion of these cells will be of use to the clinicians, which has not been successful till now, an important underlying reason being, and incomplete knowledge of the key regulatory factors. In that direction, my lab will be using mouse fetal liver (FL) as the model to uncover;

  1. How the HSC pool is created during development and what are the mechanisms involved in symmetrical divisions?
  2. What are the extrinsic regulators that maintain the state of quiescence in adult HSCs?
  3. Molecular events that regulate functional changes in HSCs during aging!
  4. Bioenergetic profile of the HSCs that leads to their differential function in different physiological states!
  5. Outside-in integrin signaling in adult and fetal hematopoiesis


Figure Legend: Events during development of hematopoietic system wherein transient sites of hematopoiesis appear before bone marrow establishes as the permanent site for adult life (Upper panel). Intrinsic as well as extrinsic factors regulate HSC function. Alteration in key regulators result in loss of stem cell function as seen during ageing processes as well as during age-associated pathological conditions (Lower panel).