Hematopoiesis - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 41

2.4.1.6 SPI1 Transcription Factor

Multipotent hematopoietic stem cells have different expression of stem cell
marker SCA1 with distinct transcriptomes: SCA1 low ,SCA1 mid ,andSCA1 high .
Both SCA1 high and SCA1 low progenitor cells express the highest and lowest
level of myeloid fate-determining transcription factor SPI1, respectively [ 75 ]. 43
Transcription factor SPI1 operates in multipotent progenitors as a selector for
development of B lymphocytes, monocytes, acrophages, and granulocytes. CCAAT/
enhancer binding protein-

that controls myeloid specification upregulates SPI1
expression. Concentration of SPI1 is indeed higher in myeloid than lymphoid
progenitors (graded expression), but transcription factors SPI1 and Ikaros are
highly expressed in lymphoid-primed multipotent progenitors. Among numerous
transcription factors that intervene during hematopoiesis, such as GATA1, MyB,
SPI1, Ikaros, bHLHb21, EBF1, and erythroid-derived nuclear factor NFe2, GATA1
and SPI1 mutually inhibit one another from committing to the erythroid or myeloid
lineage.
Transcription factor Ikaros is also required for the generation of common
lymphoid progenitors, B, natural killer, and most types of T cells. Transcription
factors TCF7 and GATA3 are critical for T-cell specification.

α

2.4.1.7 Myocyte Enhancer Factor

Transcription factor myocyte enhancer factor MEF2c that has a restricted expression
(hematopoietic stem cells, myeloid progenitors, B lymphocytes, and mature mono-
cytes) participates in lineage specification, as it promotes and suppresses lymphoid
and myeloid lineage differentiation, respectively [ 76 ].
Hematopoietic stem cells give rise to multipotent progenitors that still gen-
erate all of the blood cell lineages, then progenitors with restricted potential
such as lymphoid-primed multipotent progenitors that have lost the ability to
form megakaryocytes and erythrocytes but retain lymphoid and myelomonocytic
potential, earliest T-cell progenitors, and common lymphoid progenitors or early
lymphoid progenitors that generate B, T, and NK cells. Commitment of multipotent
progenitors toward the B-cell lineage requires MEF2c. Expression of MEF2c
depends on SPI1 transcription factor.

43 Transcription factor SPI1 is also known as PU1 factor. This tissue-specific member of the
ETS family of transcription factors is predominantly expressed in myeloid cells (granulocytes,
monocytes, and macrophages) and B lymphocytes.