Definitive hematopoietic stem/progenitor cells manifest distinct differentiation output in the zebrafish VDA and PBI

Jin, Hao; Sood, Raman; Xu, Jin; Zhen, Fenghua; English, Milton A.; Liu, Pu Paul; Wen, Zilong

doi:10.1242/dev.029637

Cited by 98 publications

(75 citation statements)

References 51 publications

(76 reference statements)

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“…This result mimicked the loss of βe1-globin in vlt m651 mutants, with the exception that βe1-globin expression persisted in the PBI (Fig. 5C, inset), as has been demonstrated for α1-globin, Scl and Gata1 (Jin et al, 2009). …”

Section: Resultssupporting

confidence: 77%

DivergentHemogengenes of teleosts and mammals share conserved roles in erythropoiesis: Analysis using transgenic and mutant zebrafish

et al. 2018

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Hemogen is a vertebrate transcription factor that performs important functions in erythropoiesis and testicular development and may contribute to neoplasia. Here we identify zebrafish Hemogen and show that it is considerably smaller (∼22 kDa) than its human ortholog (∼55 kDa), a striking difference that is explained by an underlying modular structure. We demonstrate that Hemogens are largely composed of 21-25 amino acid repeats, some of which may function as transactivation domains (TADs). Hemogen expression in embryonic and adult zebrafish is detected in hematopoietic, renal, neural and gonadal tissues. Using Tol2- and CRISPR/Cas9-generated transgenic zebrafish, we show that Hemogen expression is controlled by two Gata1-dependent regulatory sequences that act alone and together to control spatial and temporal expression during development. Partial depletion of Hemogen in embryos by morpholino knockdown reduces the number of erythrocytes in circulation. CRISPR/Cas9-generated zebrafish lines containing either a frameshift mutation or an in-frame deletion in a putative, C-terminal TAD display anemia and embryonic tail defects. This work expands our understanding of Hemogen and provides mutant zebrafish lines for future study of the mechanism of this important transcription factor.

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Section: Resultssupporting

confidence: 77%

DivergentHemogengenes of teleosts and mammals share conserved roles in erythropoiesis: Analysis using transgenic and mutant zebrafish

et al. 2018

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“…Zebrafish were maintained according to standard protocol (Westerfield, 1995 (Jin et al, 2009;Sood et al, 2010), Tg(hsp70:mCherry-T2a-CreER T2 ) #12 (Hans et al, 2011), and Tg(coro1a:loxP-DsRedx-loxP-GFP) hkztg12 lines were used in this study.…”

Section: Experimental Procedures Zebrafishmentioning

confidence: 99%

“…All images were captured by Leica SP8 confocal microscope and the quantification was done manually. The primary antibodies used in this study included Anti-GFP antibody (ab6658, Abcam), anti-Lcp1 antibody (Jin et al, 2009), and anti-hemoglobin ae1 (Jin et al, 2007). The secondary antibodies used in this study were Alexa 488-anti-goat antibody (A11055 Invitrogen), Alexa 555-anti-rabbit antibody (A31572 Invitrogen), and Alexa 647-anti-rabbit antibody (A31573 Invitrogen).…”

Section: Whole-mount In Situ Hybridizationmentioning

confidence: 99%

Temporal-Spatial Resolution Fate Mapping Reveals Distinct Origins for Embryonic and Adult Microglia in Zebrafish

et al. 2015

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Microglia are CNS resident macrophages, and they play important roles in neural development and function. Recent studies have suggested that murine microglia arise from a single source, the yolk sac (YS), yet these studies lack spatial resolution to define the bona fide source(s) for microglia. Here, using light-induced high temporal-spatial resolution fate mapping, we challenge this single-source view by showing that microglia in zebrafish arise from multiple sources. The embryonic/larval microglia originate from the rostral blood island (RBI) region, the equivalent of mouse YS for myelopoiesis, whereas the adult microglia arise from the ventral wall of dorsal aorta (VDA) region, a tissue also producing definitive hematopoiesis in mouse. We further show that the VDA-region-derived microglia are Runx1 dependent, but cMyb independent, and developmentally regulated differently from the RBI region-derived microglia. Our study establishes a new paradigm for investigating the development and function of distinct microglia populations.

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“…Time-lapse images were acquired from 1 dpi for the treated Tg(lyz:eGFP) nz117 26, and the data revealed the generation of nascent lyz-GFP + neutrophils in the niche adjacent to the CA (Fig. 2F; see supplementary Video S4), where more immature progenitors resided24. The lyz-GFP + neutrophils showed weak signals initially that gradually increased in strength, indicating differentiation of the neutrophils after challenge.…”

Section: Resultsmentioning

confidence: 95%

“…1B; see supplementary Video S1 and S2). In parallel with the disappearance of moving bacteria in the circulation, the number of large foci increased to approximately 16 in the CHT161924 at 1 day post-injection (dpi). However, this number decreased thereafter, and the bacteria almost completely disappeared by 6 dpi (Fig.…”

Section: Resultsmentioning

confidence: 99%

Systemic inoculation of Escherichia coli causes emergency myelopoiesis in zebrafish larval caudal hematopoietic tissue

Hou

Sheng

Mao

et al. 2016

Sci Rep

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Emergency granulopoiesis occurs in response to severe microbial infection. However, whether and how other blood components, particularly monocytes/macrophages and their progenitors, including hematopoietic stem/progenitor cells (HSPCs), participate in the process and the underlying molecular mechanisms remain unknown. In this study, we challenged zebrafish larvae via direct injection of Escherichia coli into the bloodstream, which resulted in systemic inoculation with this microbe. The reaction of hematopoietic cells, including HSPCs, in the caudal hematopoietic tissue was carefully analysed. Both macrophages and neutrophils clearly expanded following the challenge. Thus, emergency myelopoiesis, including monopoiesis and granulopoiesis, occurred following systemic bacterial infection. The HSPC reaction was dependent on the bacterial burden, manifesting as a slight increase under low burden, but an obvious reduction following the administration of an excessive volume of bacteria. Pu.1 was important for the effective elimination of the microbes to prevent excessive HSPC apoptosis in response to stress. Moreover, Pu.1 played different roles in steady and emergency monopoiesis. Although Pu.1 was essential for normal macrophage development, it played suppressive roles in emergency monopoiesis. Overall, our study established a systemic bacterial infection model that led to emergency myelopoiesis, thereby improving our understanding of the function of Pu.1 in this scenario.

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Definitive hematopoietic stem/progenitor cells manifest distinct differentiation output in the zebrafish VDA and PBI

Cited by 98 publications

References 51 publications

DivergentHemogengenes of teleosts and mammals share conserved roles in erythropoiesis: Analysis using transgenic and mutant zebrafish

DivergentHemogengenes of teleosts and mammals share conserved roles in erythropoiesis: Analysis using transgenic and mutant zebrafish

Temporal-Spatial Resolution Fate Mapping Reveals Distinct Origins for Embryonic and Adult Microglia in Zebrafish

Systemic inoculation of Escherichia coli causes emergency myelopoiesis in zebrafish larval caudal hematopoietic tissue

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