Abstract (hsc full form)

 

Abstract (hsc full form)

The mammalianblood System comprises more than ten different types of mature cells, is based on one cell type: hematopoietic stem cell (HSC). Within the system there are only HSC are able to exhibit self-renewal and multi-potency. Multi-potency is the capacity to differentiate into all functional blood cells. Self-renewal can give rise to HSC that is not differentiated. Since mature blood cells are typically short lived, HSC continuously provide more differentiated progenitors while properly maintaining the HSC size appropriately throughout their lives by precisely the balance between self-renewal as well as differentiation. Therefore, understanding the mechanism of self-renewal and differentiation of HSC is a key issue. In this review, we focus on the hierarchical structure of the hematopoietic system, our current understanding of the molecular and microenvironmental cues that regulate self-renewal and differentiation of the adult HSC, and the currently emerging systems approaches to understand HSC Biology. Go to:

Introduction

Although adult blood cells produced in a rate of more 1 million cell every second in the adult human Human 1], the majority of hematopoietic stem cells (hscs) from which they derive have a very limited cycle and reside at the G 0 phase of the cell cycle under healthy conditions [2]. The two facts presented here create an intriguing dilemma: how dose the organism achieve an equilibrium where a sufficient supply of hscs is maintained throughout the life of the organism, and at the same time HSCs constantly meet the huge need for constant replenishment of adult blood cells most of which have a short lifespan. The significance of this equilibrium is demonstrated by the many instances where the abnormal growth of HSCs causes serious diseases e.g. when HSC differentiation into committed progenitors is not accompanied by the normal loss of self-renewal capability, or progenitors derived from HSCs fail to fully differentiate to mature blood cells [ 3or enter a preleukemic progression [ 44. These fascinating aspects of mammalian hemopoiesis have led to a vast research into the process over the last couple of decades. In this review, we focus on the outlined conundrum, and examine what is known about the regulatory mechanisms that control the capacity of HSCs to produce millions of blood-forming mature cells, while at the same time maintaining an adequate supply of HSCs throughout the life span of the species. Go to:

The Concept of Stem Cells

The "stem cell" concept was initially proposed through Till and McCulloch following their pioneering studies on the blood system's regeneration in the vivo. Ten days after transplanting a limited number of syngenic bone marrow (BM) cells to recipient mice, they observed cells that had formed in the spleens of recipients mice. Examining these colonies revealed that a small portion of the donors BM cells had two unique characteristics: (1) the ability to produce multiple kinds of myeloerythroid cell, and (2) the ability to self-replicate [ 5- 81 1. These results revealed the two defining criteria of stem cells i.e. multi-potency and self-renewal. Hematopoietic Stem Cells (HSCs) are the only cells of the hematopoietic system with the potential for both multi-potency and self-renewal. For HSC Multi-potency refers to the capacity to differentiate into any functional blood cell, while self-renewal refers to the ability to give rise to identical daughter HSCs that do not differentiate.

The field of stem cell research has expanded significantly since the first studies by Till as well as McCulloch and includes stem cells that contribute to specific organs/tissues (collectively named tissue-specific stem cell) as well as embryonic stem (ES) cells that can give rise to every kind of cell in the adult body. A system of nomenclaturehas been developed to indicate the possibility of differentiation of different kinds of stem cell (summarized as Table 1). It is not within our scope to explore non-hematopoietic stem cell populations; great reviews of these cells can be found throughout this publication.

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