Hematopoiesis - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 38

Tabl e 2. 8. E-protein-dependent genes in B and T lymphocytes, plasmacytoid dendritic cells and
their multipotent progenitors ( Part 2 ; Source: [ 70 ]).

Cell Genes expressed prior to

type lineage restriction

Lymphoid-primed

Hematopoietic

multipotent progenitors stem cells

B lymphocyte Rag2, IL7RA, Ets1 Igh, Dntt

T lymphocyte Rag2, IL7RA, Ets1 Notch-1, Dntt

Plasmacytoid Ccr9, Dntt

Dendritic cell

Transcription factors bHLHb19 to bHLHb21 participate in B-cell development
before preB-cell receptor expression [ 70 ]. They also promote survival of proB cells
(committed B-cell progenitors), as they prevent caspase-2 activation. They regu-
late the transcription of RAG1 and RAG2 recombination-activating genes. They
cooperates with signal transducer and activator of transcription STAT5 to activate
cell cycle regulators of the family of cellular myelocytomatosis viral-related proto-
oncogene products cellular MyC and neuroblastoma-derived nMyc to support
cytokine-dependent proliferation.
Transcription factors bHLHb19 to bHLHb21 operate in T-cell progenitor cells
to control expression of T-cell receptor

chain (Fig. 2.3 ). Transcription factors
bHLHb21 E12 and bHLHb21 E47 operate in the transcriptional regulation that fosters
commitment to and differentiation of B- and T-cell lineages [ 70 ]. They are required
for development of lymphoid-primed multipotent progenitors from hematopoietic
stem cells. 38 However, they prevent the proliferation of hematopoietic stem cells and
lymphoid-primed multipotent progenitors. They target lymphoid genes. They acti-
vate early B-cell factor EBF1 to promote B-cell lineage specification and cooperate
with transcription factors EBF1 and Paired box protein Pax5 to activate many B-cell
lineage-associated genes [ 70 ]. In addition, TcF4 intervenes in the development of
mature plasmacytoid dendritic cells, in which it regulates transcription of multiple
lymphoid-associated genes.
Proteins of the E2A family, bHLHb21 E12 and bHLHb21 E47 , regulate Notch-1
expression in early thymic progenitors and collaborate with Notch-1 to excite
Notch-1 target genes (e.g., hairy and enhancer of split HES1 (or bHLHb39),
preT-cell receptor

β

chain [PTCRA], etc.) [ 70 ]. The Hes1 gene is needed for T-
cell progenitor expansion. Conversely, Notch-1 inhibits E2A protein. In addition,
transcription factor Paired box protein Pax5, a partner of TcF2

α

and TcF3, represses
Notch-1 transcription, thereby preventing T-cell fate in proB cells.

α

38 The lymphoid-primed multipotent progenitor pool is a subset of LIN − ,SCFR + ,SCA1 + cells
that express STK1 kinase (or FMS-related Tyr kinase FLT3). They have the potential to develop
into granulocytes, lymphocytes, and monocytes, but neither erythrocytes nor megakaryocytes.