Hematopoiesis - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 39

HSC

self−renewal

bHLHb21

lymphoid and myeloid
restriction ETP LMPP

lymphoid
restriction

CLP

DN2 proDC

bHLHb20

DN3 prepDC proB NKP commtiment

E2−2

bHLHb26

−

T cell pDC B cell NK cell differentiation

Fig. 2.3 Transcription factors of the E and ID categories (i.e., bHLHb19-bHLHb21 and
bHLHb24-bHLHb27) in lymphoid lineage commitment (Source: [ 70 ]). Formation of B, T,
natural killer (NK), and plasmacytoid dendritic (pDC) cells from hematopoietic stem cell
(HSC), lymphoid-primed multipotent progenitor (LMPP), early thymic progenitor (ETP), common
lymphoid progenitor (CLP), double-negative (DN) and NK cell progenitor (NKP). Self-renewal of
stem cells and proliferation of some progenitors happens in the absence of E2A proteins. Proteins
of the E2A set enforce the -selection checkpoint during T-cell development. DN3 cells express a

preT-cell receptor owing to recombination-activating RAG1 gene. In the absence of E2A protein,
DN3 cells proceed past the

β

thymocytes. On
the other hand, B-cell development happens when E2A protein level decays. However, bHLHb19
(TcF4) is required in plasmacytoid dendritic cell development. Inhibitor of DNA binding ID2 (or
bHLHb26) that antagonizes E proteins is involved in the development of mature natural killer cells,
as well as optimal formation of subsets of conventional dendritic cells, such as CD8 − , CD11c +
dendritic cells and Langerhans cells, whereas it prevents plasmacytoid dendritic cell development.

β -selection checkpoint and become CD4 + ,CD8 +

Transcription factors bHLHb21 E12 and bHLHb21 E47 target recombination-
activating gene Rag1, terminal deoxynucleotidyltransferase gene (Dntt), and
immunoglobulin heavy chain gene Igh6 regulate multipotent progenitors for the
formation of common lymphoid progenitors.
Transcription factors bHLHb21 E12 and bHLHb21 E47 , Early B-cell factor EBF1,
and Pax5 engage hematopoietic progenitors to the B-cell lineage. Transcription
factors bHLHb21 E12 and bHLHb21 E47 heterodimerize with bHLHa17 expressed in
mesodermal cells that develop into embryonic blood cells as well as fetal and adult
hematopoietic stem cells.
Activated bHLHb21 E12 bHLHb21 E47 and act in synergy with SPI1 and

interleukin-7 receptor IL7R that activates signal transducer and activator of

transcription STAT5 to induce EBF1 transcription that, in turn, activates Pax5
expression. Proteins bHLHb21 E12 and bHLHb21 E47 with EBF1 and Pax5 activate
many B-cell-associated genes. In hematopoietic stem cells, bHLHb21 E12 and
bHLHb21 E47 promote development of the entire spectrum of early hematopoietic
progenitors [ 54 ]. They favor the maturation of myelolymphoid and myelo-erythroid
progenitors.

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