Tissue

Biology, embryology, histopathology, and pathology of the tissues that constitute multicellular organisms.

hematopoiesis

Hematopoiesis is the production of blood cells, a developmental process located in the (red) bone marrow, though some cells mature elsewhere. For example, T lymphocytes are so named because they mature in the thymus, and antigenic stimulation of B lymphocytes to become plasma cells typically takes place in the periphery.

The process of haematopoiesis occurs in several stages, and is controlled by at least 11 growth factors. The first stage involves the differentiation of a pluripotential stem cell into a committed progenitor, which is followed by maturation of committed progenitors in distinct pathways.


Stem cell stage:
pluripotential hematopoietic stem cell
--------------------

The common myeloid progenitor can generate:

● proerythroblasts (pronormoblasts) → erythropoiesis

● myeloblasts → granulopoiesis

● monoblasts → monocytopoiesis

● megakaryoblasts → thrombopoiesis

The common lympoid progenitor can generate:

● lymphoblasts → lymphopoiesis

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Committed progenitor stage to mature cell : granulopoiesis

common myeloid progenitor

myeloblast

B/E/N promyelocyte

------

B/E/N myelocyte

------

B/E/N metamyelocyte

------

B/E/N band

------

basophil, eosinophil, neutrophil

-----------------------

mast cell -----------------------

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Committed progenitor stage to mature cell : lymphopoiesis

common lymphoid progenitor

lymphoblast

----------------------------------------↓ rearrangements H: D-J → H: V-DJ

prolymphocyte

-----------------↓ rearrangements L: V-J --------------------------

small lymphocyte------or----- natural killer cell (large granular lymphocyte)

------------↓ IgM→IgD ---------------------------------------------

------B lymphocyte--or-- T lymphocyte

-----------------------------------------------------------------------

--------plasma cell------------------------------------------lymphoid dendritic cell

Development of mature B lymphocytes from multipotent progenitors requires the coordinated activities of a number of transcriptional regulatory proteins, including EBF, Pax-5, and E2A.

E2A proteins function in early B lineage development to regulate B lineage-specific gene expression as well as B cell survival. E2A-encoded proteins are involved in the differentiation of a number of cell types, and they are especially important in lymphocyte development.

The E2A gene encodes E47 and E12, which are basic-helix-loop-helix (bHLH) transcription factors that bind DNA either as homodimers or as heterodimers with other bHLH proteins. Such bHLH DNA binding activity in the B-lineage comprises E47 homodimers. Development of thymocytes mainly involves heterodimers of E47 and a related bHLH protein, HEB. Thymocytic E2A protein expression is required to initiate T-cell differentiation. During the development of thymoctyes, E-proteins and their antagonists, Id2 and Id3, regulate T-lineage specific gene expression and TCR rearrangement. E2A and Id proteins block thymocytic maturation in the absence of pre-TCR expression, and pre-TCR signaling acts to promote development in part by inhibiting E2A activity. [l]

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Committed progenitor stage to mature cell : monocytopoiesis

common myeloid progenitor

monoblast

promonocyte

monocyte

----

macrophage or myeloid dendritic cell


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Committed progenitor stage to mature cell : erythropoiesis

common myeloid progenitor

proerythroblast

basophilic erythroblast

polychromatic erythroblast

polychromatic erythrocyte (reticulocyte)

erythrocyte (RBC)

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Committed progenitor stage to mature cell : thrombopoiesis

megakaryoblast
promegakaryocyte
megakaryocyte
thrombocytes (platelets)


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