**Part 1**

**Hematopoietic Stem Cell Properties** 

**1** 

*Brazil* 

**Networks Establishing Hematopoietic Stem Cell** 

Hematopoiesis is a tightly regulated process maintained by a small pool of hematopoietic stem cells (HSC) capable of undergoing self-renewal and generating mature progeny of all of the hematopoietic cell lineages. To sustain the proper levels of blood cells, HSCs must continuously monitor and regulate the balance between self-renewal and lineage differentiation. To produce all hematopoietic cells, hematopoiesis proceeds in a step-wise manner from the primordial long-term (LT)-HSCs. LT-HSCs possess the ability to self-renew and the capacity for long-term reconstitution of lethally irradiated hosts. After a first step of differentiation, LT-HSCs lose their capacity for self-renewal and give rise to a population of short-term (ST)-HSCs. The ST-HSCs has a limited ability to self-renew and reconstitute lethally irradiated hosts, but differentiate into a multipotent progenitor (MPP) population. The MPPs lack the capacity to undergo self-renewal, but retain multipotency. From these multipotent progenitors develops a series of intermediate progenitors that give rise to the assorted hematopoietic lineages. In the classical pathway of hematopoiesis, these intermediates include the common lymphoid progenitors (CLPs) that differentiate into lymphoid, but not myeloid progeny, and the common myeloid progenitors (CMPs), which retain full erythromyeloid potential. The CMPs further differentiate to form the granulocyte/macrophage progenitors (GMPs) that differentiate to the myelomonocytic lineage and the megakaryocytic/erythrocyte progenitors (MEPs) that eventually differentiate to form red blood cells and platelets. All these blood cells produced daily in high numbers (1 × 1012 cells/day) are derived from a relatively small but rare fraction of

Transcriptional regulation is a key mechanism controlling HSC homeostasis, development,

Hematopoiesis is regulated at the level of pluripotent HSCs and committed progenitors through growth and/or differentiation inducing factors (like EPO, G-CSF, GM-CSF, IL-1, IL-3) that interact with receptors and initiate signal transduction processes that culminate in the activation of new genetic programs. These external stimuli trigger intrinsic determinants of cell fate, the transcription factors which contribute to the reprogramming of HSCs into cell-

**1. Introduction** 

multipotent cells, the HSCs (Weissman, 2000).

**2. Transcription factors in hematopoietic development** 

and lineage commitment.

**Multipotency and Self-Renewal** 

*Instituto Nacional de Câncer, Rio de Janeiro,* 

Eliana Abdelhay, Luciana Pizzatti and Renata Binato
