Epigenetic control of dendritic cell development and fate determination of common myeloid progenitor by Mysm1

Won, Haejung; Nandakumar, Vijayalakshmi; Yates, Peter; Sanchez, Suzi; Jones, Lindsey; Huang, Xue F.; Chen, Si-Yi

doi:10.1182/blood-2013-10-534313

Cited by 43 publications

(64 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…controversial (23,56,59), we previously demonstrated its presence and function (15,20,44), and we confirmed its presence by real-time PCR in the present study in mouse liver tissue (data not shown). We acknowledge that several signaling pathways are likely to be involved in this phenomenon.…”

Section: Discussionsupporting

confidence: 94%

Mitigation of autophagy ameliorates hepatocellular damage following ischemia-reperfusion injury in murine steatotic liver

Gupta

Kolachala

Jiang

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Ischemia-reperfusion injury (IRI) is a common clinical consequence of hepatic surgery, cardiogenic shock, and liver transplantation. A steatotic liver is particularly vulnerable to IRI, responding with extensive hepatocellular injury. Autophagy, a lysosomal pathway balancing cell survival and cell death, is engaged in IRI, although its role in IRI of a steatotic liver is unclear. The role of autophagy was investigated in high-fat diet (HFD)-fed mice exposed to IRI in vivo and in steatotic hepatocytes exposed to hypoxic IRI (HIRI) in vitro. Two inhibitors of autophagy, 3-methyladenine and bafilomycin A1, protected the steatotic hepatocytes from HIRI. Exendin 4 (Ex4), a glucagon-like peptide 1 analog, also led to suppression of autophagy, as evidenced by decreased autophagy-associated proteins [microtubule-associated protein 1A/1B-light chain 3 (LC3) II, p62, high-mobility group protein B1, beclin-1, and autophagy-related protein 7], reduced hepatocellular damage, and improved mitochondrial structure and function in HFD-fed mice exposed to IRI. Decreased autophagy was further demonstrated by reversal of a punctate pattern of LC3 and decreased autophagic flux after IRI in HFD-fed mice. Under the same conditions, the effects of Ex4 were reversed by the competitive antagonist exendin 9-39. The present study suggests that, in IRI of hepatic steatosis, treatment of hepatocytes with Ex4 mitigates autophagy, ameliorates hepatocellular injury, and preserves mitochondrial integrity. These data suggest that therapies targeting autophagy, by Ex4 treatment in particular, may ameliorate the effects of IRI in highly prevalent steatotic liver.

show abstract

Section: Discussionsupporting

confidence: 94%

Mitigation of autophagy ameliorates hepatocellular damage following ischemia-reperfusion injury in murine steatotic liver

Gupta

Kolachala

Jiang

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…S2 and S3). Because Mysm1 knockout does not affect the global ubH2A level, Mysm1 may control hematopoiesis (B-cell development, CLP fate determination, and natural killer cell maturation) by targeting a limited number of genes (23,24,39,40). Increased reactive oxygen species, γ-H2AX foci, and p53 level were observed in Mysm1 KO HSCs (23).…”

Section: Discussionmentioning

confidence: 99%

The histone H2A deubiquitinase Usp16 regulates hematopoiesis and hematopoietic stem cell function

Jones

Yang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Epigenetic mechanisms play important regulatory roles in hematopoiesis and hematopoietic stem cell (HSC) function. Subunits of polycomb repressive complex 1 (PRC1), the major histone H2A ubiquitin ligase, are critical for both normal and pathological hematopoiesis; however, it is unclear which of the several counteracting H2A deubiquitinases functions along with PRC1 to control H2A ubiquitination (ubH2A) level and regulates hematopoiesis in vivo. Here we investigated the function of Usp16 in mouse hematopoiesis. Conditional deletion of Usp16 in bone marrow resulted in a significant increase of global ubH2A level and lethality. Usp16 deletion did not change HSC number but was associated with a dramatic reduction of mature and progenitor cell populations, revealing a role in governing HSC lineage commitment. ChIP- and RNA-sequencing studies in HSC and progenitor cells revealed that Usp16 bound to many important hematopoietic regulators and that Usp16 deletion altered the expression of genes in transcription/chromosome organization, immune response, hematopoietic/lymphoid organ development, and myeloid/leukocyte differentiation. The altered gene expression was partly rescued by knockdown of PRC1 subunits, suggesting that Usp16 and PRC1 counterbalance each other to regulate cellular ubH2A level and gene expression in the hematopoietic system. We further discovered that knocking down Cdkn1a (p21cip1), a Usp16 target and regulated gene, rescued the altered cell cycle profile and differentiation defect of Usp16-deleted HSCs. Collectively, these studies identified Usp16 as one of the histone H2A deubiquitinases, which coordinates with the H2A ubiquitin ligase PRC1 to regulate hematopoiesis, and revealed cell cycle regulation by Usp16 as key for HSC differentiation.

show abstract

“…6 MYSM1 was also shown to regulate the differentiation of multiple hematopoietic lineages by activating Ebf1, Id2, or Flt3 transcription. 2,4,7 Nevertheless, the significance of p53 elevation in Mysm1 2/2 hematopoiesis has not been addressed. p53 is a central regulator of cellular stress responses.…”

Section: Introductionmentioning

confidence: 99%

p53 mediates loss of hematopoietic stem cell function and lymphopenia in Mysm1 deficiency

Belle

Langlais

Petrov

et al. 2015

Blood

View full text Add to dashboard Cite

show abstract

Epigenetic control of dendritic cell development and fate determination of common myeloid progenitor by Mysm1

Abstract: Key Points Deletion of Mysm1 impairs development of steady-state DC, but no other myeloid lineages; monocyte, macrophage, and granulocyte. Mysm1 governs DC differentiation from CMP by regulating Flt3 expression via modulating histone modifications and mediating Pu.1 recruitment.

Cited by 43 publications

References 41 publications

Mitigation of autophagy ameliorates hepatocellular damage following ischemia-reperfusion injury in murine steatotic liver

Mitigation of autophagy ameliorates hepatocellular damage following ischemia-reperfusion injury in murine steatotic liver

The histone H2A deubiquitinase Usp16 regulates hematopoiesis and hematopoietic stem cell function

p53 mediates loss of hematopoietic stem cell function and lymphopenia in Mysm1 deficiency

Contact Info

Product

Resources

About