Stem Cell Microenvironments and Beyond

(Wang) #1
45

30-48 hpf
HSC mobilization

DA

CV

B.

A.

HSC engraftment
48-72 hpf

CHT

AGM/DA

Endotomal-derived
Cell

Macrophage
Hemogenic
Endothelial Cell

HSC

Cxcl12 c-MybCbfβ

CVP
CHT

CV

Somite-derived
Stromal Cell

Cxcl8

G-csf

CA

HSC daughter
Cell

Nik, Weinreb and Bowman Figure 3

Fig. 4.3 Signals and cell types regulating developmental HSC mobilization and engraftment. (a)
The left diagram shows the position within the zebrafish shown in the cross-section (right). The
right panel highlights the most recent findings on the niche cells and signaling pathways involved
in HSC mobilization/migration from the DA. Expression of the transcription factors c-Myb and
Cbfβ in emerging HSCs is important to mediate egress from the DA. Appropriate levels of Cxcl12
are required for this process, and are regulated by endotomal-derived endothelial cells and HSC
expression of c-Myb. Macrophages serve as escorts that facilitate HSC migration into the CV. (b)
The left diagram shows the position within the zebrafish shown in the cross-section (right). The
right panel highlights the most recent findings on the niche cells and signaling pathways involved
in HSC engraftment in the CHT niche. Within the CHT, HSCs are surrounded by endothelial cells
and contact a stromal cell, which provides cues on the orientation of the division plane. The stro-
mal cells are derived from the somite and are critical for HSC maintenance in the CHT niche.
Secreted factors, such as Cxcl8 and G-csf modify HSC interactions and proliferation within the
niche. HSC hematopoietic stem cell, NC notochord, DA dorsal aorta, CV caudal vein, Cxcl12-CXC
chemokine ligand 12, Cbfβ core binding protein beta, CA caudal artery, CVP caudal vein plexus,
CHT caudal hematopoietic tissue, Cxcl8-CXC chemokine ligand 8, Gcsf granulocyte-colony stim-
ulating factor


4 Developmental HSC Microenvironments: Lessons from Zebrafish

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