Hematopoiesis - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 32

Numerous substances regulate hematopoiesis using a specific set of transcription
factors. They include morphogens and growth factors (Table 2.4 )thatprime
signaling cascades with given effectors down to transcription factors for gene
expression. In addition, hematopoietic stem cells are mobilized by the sympathetic
nervous system.
Under normal conditions, bone morphogenetic proteins, osteopontin, 23 Wnt in-
hibitors secreted Frizzled-related proteins sFRP1, and non-canonical Wnts are
expressed in the endosteal zone to yield an inhibitory microenvironment to favor
the pool of long-term quiescent hematopoietic stem cells [ 40 ].
On the other hand, fibroblast growth factors, canonical Wnt signals, and CXCL12
expressed from endothelial, megakaryocytic, and CXCL12 high reticular cells stimu-
late the active subpopulation of hematopoietic stem cells in the central zone.

2.4.1 Transcription Factors of Hematopoiesis

Transcriptional regulation controls and maintains the hematopoietic stem cell pool
in the bone marrow as well as lineage commitment. Transcription factors of the
E protein family (TcF3, TcF4, and TcF12), i.e., bHLHb19 to bHLHb21 (Table 2.5 ),
and inhibitors of DNA-binding (ID), i.e., bHLHb24 to bHLHb27, which are
synthesized in hematopoietic cells, regulate many developmental processes.
Progenitor fate depends on coordinated activities of multiple transcription
factors, such as Activator protein AP1, CCAAT/enhancer-binding protein C/EBP

,
early B-cell factor EBF1, erythroid differentiation-associated gene product (EDAG),
or hemogen, 24 erythroid Kr uppel-like factor (KLF1 or EKLF), members of the
GATA family, zinc finger protein multitype ZFPM1, 25 and Paired box protein Pax5.

α

2.4.1.1 GATA Transcription Factors

The transcription factors, GATA-binding factors, interact with ZFPM1 to activate
or repress transcription during tissue development. Hematopoietic factor GATA1
activates all known erythroid and megakaryocyte-specific genes, but represses
GATA2, SCFR, and MyC genes. 26

23 A.k.a. bone sialoprotein BSP1, early T-lymphocyte activation ETA1, and secreted phosphopro-
tein SPP1.
24 A.k.a. hemopoietic gene protein and negative differentiation regulator (NDR).
25 A.k.a. friend of GATA protein FOG1, zinc finger domain-containing protein ZnF89a and
ZnF408.
26 The family of MYC genes that encode subclass-E basic helix-loop-helix proteins encompasses:
(1) cellular (MYC or CMYC [bHLHe39]); (2) small cell lung carcinoma-derived (LMYC
[bHLHe38]); and (3) neuroblastoma-derived (NMYC [bHLHe37]) genes. The MYC gene has been
discovered in patients with Burkitt lymphoma.