Plasticity and Maintenance of Hematopoietic Stem Cells During Development

Abstract

Maintenance of hematopoietic stem cells (HSCs) pool depends on fine balance between self-renewal and differentiation of HSCs. HSCs normally reside within the bone marrow niche of an adult mammal. The embryonic development of HSCs is a complex process that involves the migration of developing HSCs in multiple anatomical sites. Throughout the process, developing HSCs receive internal (transcriptional program) and external (HSC niche) signals, which direct them to maintain balance between self-renewal and differentiation, also to generate a pool of HSCs. In physiological condition HSCs differentiate into all mature cell types present in the blood. However, in pathological condition they may differentiate into non-hematological cells according to the need of the body. It was shown that HSCs can transdifferentiate into cell types that do not belong to the hematopoietic system suggests a complete paradigm shift of the hierarchical hematopoietic tree. This review describes the developmental origins and regulation of HSCs focusing on developmental signals that induce the adult hematopoietic stem cell program, as these informations are very critical for manipulating conditions for expansion of HSCs in ex vivo condition. This review also states clinical application and related patents using HSC.

Hematopoietic stem cells: An overview

“…The fetal liver is the site of hematopoiesis during early embryonal development. At 14-20 weeks of gestation, the bone marrow is seeded with stem cells from the liver and spleen and is responsible for blood cell generation during postnatal phase [5,[13][14][15][16][17][18][19][20][21][22].…”

“…The relative number of CD34+ cells in the collections of cord blood declined with gestational age, but expression of celladhesion molecules on these cells increased (i.e. preparations for the cells to relocate from homing in fetal liver to homing in bone marrow) [8,19,20,23]. Table 1 shows some differences between fetal and adult HSC.…”

“…The main hypotheses are hemangioblasts or hemogenic endothelial [4]. Old theory proposes that primitive erythrocytes and endothelial cells were closely associated physically and they have a common mesodermal precursor called hemangioblast [19]. The younger theory proposes that HSCs originate from a subset of early endothelial cells known as hemogenic endothelium.…”

“…All these oligopotent progenitors differentiate into their restricted lineage commitment: (1) CMPs advance to megakaryocyte/erythrocyte progenitors (MEPs), granulocyte/macrophage progenitors (GMPs), and dendritic cell (DC) progenitors; (2) CLPs give rise to T cell progenitors, B cell progenitors, NK cell progenitors and DC progenitors. Notably, DC progenitors (CD8+ DC, CD8− DC, and plasmacytoid DC) could be derived from both CMPs and CLP [4,17,19].…”

“…This microenvironment keeps the stem cell at quiescence for its self-renewal most of the time and activates the stem cell for proliferation and tissue turnover, and/or injury repair [19]. Thus, to maintain stem Table 2 The proposed cell-surface markers for identifying HSC and its progenitors.…”