Limits...
Sumoylation of CCAAT/enhancer-binding protein α is implicated in hematopoietic stem/progenitor cell development through regulating runx1 in zebrafish.

Yuan H, Zhang T, Liu X, Deng M, Zhang W, Wen Z, Chen S, Chen Z, de The H, Zhou J, Zhu J - Sci Rep (2015)

Bottom Line: Impairment of sumoylation attenuates HSPC generation and proliferation.The hyposumoylation triggered HSPC defects are CCAAT/enhancer-binding protein α (C/ebpα) dependent.While C/ebpα-dependent transcription is involved in myeloid differentiation, our studies here reveal that C/ebpα sumoylation is essential for HSPC development during definitive hematopoiesis.

View Article: PubMed Central - PubMed

Affiliation: CNRS-LIA124, Sino-French Research Center for Life Sciences and Genomics, State Key Laboratory of Medical Genomics, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

ABSTRACT
The small ubiquitin-related modifier (SUMO) participates in various cellular processes, including maintenance of genome integrity, nuclear transport, transcription and signal transduction. However, the biological function of sumoylation in hematopoiesis has not been fully explored. We show here that definitive hematopoietic stem/progenitor cells (HSPCs) are depleted in SUMO-deficient zebrafish embryos. Impairment of sumoylation attenuates HSPC generation and proliferation. The hyposumoylation triggered HSPC defects are CCAAT/enhancer-binding protein α (C/ebpα) dependent. Critically, a SUMO-C/ebpα fusion rescues the defective hematopoiesis in SUMO-deficient embryos, at least in part through restored runx1 expression. While C/ebpα-dependent transcription is involved in myeloid differentiation, our studies here reveal that C/ebpα sumoylation is essential for HSPC development during definitive hematopoiesis.

No MeSH data available.


Multiple blood cell lineages are impaired in SUMO-deficient embryos.(A–I) WISH assays of lysozyme C (A–C), hbae1 (D–F) and rag1 (G–I) at 5 dpf. Boxed regions indicate the CHT (A–F). (A′–F′) Magnified images of corresponding boxed regions from A to F, respectively. Blue arrows identify lysozyme C-positive cells in the CHT (A′–C′). Red arrows identify hbae1-positive cells in the CHT (D′–F′). Black arrows identify rag1-positive cells in the thymus (G–I).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4355724&req=5

f2: Multiple blood cell lineages are impaired in SUMO-deficient embryos.(A–I) WISH assays of lysozyme C (A–C), hbae1 (D–F) and rag1 (G–I) at 5 dpf. Boxed regions indicate the CHT (A–F). (A′–F′) Magnified images of corresponding boxed regions from A to F, respectively. Blue arrows identify lysozyme C-positive cells in the CHT (A′–C′). Red arrows identify hbae1-positive cells in the CHT (D′–F′). Black arrows identify rag1-positive cells in the thymus (G–I).

Mentions: To further confirm that HSPCs were depleted in SUMO-deficient embryos, lineage-specific markers related to definitive hematopoiesis were examined. Expression of the myeloid lineage marker lysozyme C and erythroid lineage marker hbae1 were drastically decreased in both SUMOs and Ubc9 morphants (Fig. 2 A–F). Expression of the lymphoid lineage marker rag1 was absent in the developing thymus compared with control siblings (Fig. 2 G–I). Thus, these results demonstrate that the three major definitive hematopoitic lineages are all compromised in SUMO-deficient embryos.


Sumoylation of CCAAT/enhancer-binding protein α is implicated in hematopoietic stem/progenitor cell development through regulating runx1 in zebrafish.

Yuan H, Zhang T, Liu X, Deng M, Zhang W, Wen Z, Chen S, Chen Z, de The H, Zhou J, Zhu J - Sci Rep (2015)

Multiple blood cell lineages are impaired in SUMO-deficient embryos.(A–I) WISH assays of lysozyme C (A–C), hbae1 (D–F) and rag1 (G–I) at 5 dpf. Boxed regions indicate the CHT (A–F). (A′–F′) Magnified images of corresponding boxed regions from A to F, respectively. Blue arrows identify lysozyme C-positive cells in the CHT (A′–C′). Red arrows identify hbae1-positive cells in the CHT (D′–F′). Black arrows identify rag1-positive cells in the thymus (G–I).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4355724&req=5

f2: Multiple blood cell lineages are impaired in SUMO-deficient embryos.(A–I) WISH assays of lysozyme C (A–C), hbae1 (D–F) and rag1 (G–I) at 5 dpf. Boxed regions indicate the CHT (A–F). (A′–F′) Magnified images of corresponding boxed regions from A to F, respectively. Blue arrows identify lysozyme C-positive cells in the CHT (A′–C′). Red arrows identify hbae1-positive cells in the CHT (D′–F′). Black arrows identify rag1-positive cells in the thymus (G–I).
Mentions: To further confirm that HSPCs were depleted in SUMO-deficient embryos, lineage-specific markers related to definitive hematopoiesis were examined. Expression of the myeloid lineage marker lysozyme C and erythroid lineage marker hbae1 were drastically decreased in both SUMOs and Ubc9 morphants (Fig. 2 A–F). Expression of the lymphoid lineage marker rag1 was absent in the developing thymus compared with control siblings (Fig. 2 G–I). Thus, these results demonstrate that the three major definitive hematopoitic lineages are all compromised in SUMO-deficient embryos.

Bottom Line: Impairment of sumoylation attenuates HSPC generation and proliferation.The hyposumoylation triggered HSPC defects are CCAAT/enhancer-binding protein α (C/ebpα) dependent.While C/ebpα-dependent transcription is involved in myeloid differentiation, our studies here reveal that C/ebpα sumoylation is essential for HSPC development during definitive hematopoiesis.

View Article: PubMed Central - PubMed

Affiliation: CNRS-LIA124, Sino-French Research Center for Life Sciences and Genomics, State Key Laboratory of Medical Genomics, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

ABSTRACT
The small ubiquitin-related modifier (SUMO) participates in various cellular processes, including maintenance of genome integrity, nuclear transport, transcription and signal transduction. However, the biological function of sumoylation in hematopoiesis has not been fully explored. We show here that definitive hematopoietic stem/progenitor cells (HSPCs) are depleted in SUMO-deficient zebrafish embryos. Impairment of sumoylation attenuates HSPC generation and proliferation. The hyposumoylation triggered HSPC defects are CCAAT/enhancer-binding protein α (C/ebpα) dependent. Critically, a SUMO-C/ebpα fusion rescues the defective hematopoiesis in SUMO-deficient embryos, at least in part through restored runx1 expression. While C/ebpα-dependent transcription is involved in myeloid differentiation, our studies here reveal that C/ebpα sumoylation is essential for HSPC development during definitive hematopoiesis.

No MeSH data available.