CD166 regulates human and murine hematopoietic stem cells and the hematopoietic niche

Chitteti, Brahmananda R.; Kobayashi, Michihiro; Cheng, Ying‐Hua; Zhang, Huajia; Poteat, Bradley; Broxmeyer, Hal E.; Pelus, Louis M.; Hanenberg, Helmut; Zollman, Amy; Kamocka, Malgorzata M.; Carlesso, Nadia; Cardoso, Angelo A.; Kacena, Melissa A.; Srour, Edward F.

doi:10.1182/blood-2014-03-565721

Cited by 59 publications

(85 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…3,4 We also showed that this activity is inversely correlated with osteoblast maturation and the level of CD166 expression 4,5 which is a functional marker of murine and human HSCs and niche competency. 6 Our group also demonstrated that megakaryocytes can increase osteoblast proliferation in vitro and in vivo, [7][8][9] thus implicating megakaryocytes, albeit indirectly, in HSC maintenance. These observations identified critical interactions between osteoblasts and megakaryocytes and offered a unique experimental model to assess how megakaryocytes impact HSC function via osteoblasts.…”

Section: Introductionmentioning

confidence: 91%

“…Whether these cells (or a different subfraction of OMs) are responsible for the functional properties of OM requires additional investigations. Because we previously demonstrated that CD166 is expressed on HSCs and is critical to the competence of the hematopoietic niche, 6 it is possible that OMs contribute to the fitness of the niche through CD166-CD166 homotypic interactions. It is not clear at present if these homotypic interactions actually take place or whether they involve OMs and HSCs.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Osteomacs interact with megakaryocytes and osteoblasts to regulate murine hematopoietic stem cell function

Mohamad¹,

Xu²,

Ghosh³

et al. 2017

Blood Advances

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Osteomacs interact with megakaryocytes and osteoblasts to regulate murine hematopoietic stem cell function

Mohamad¹,

Xu²,

Ghosh³

et al. 2017

Blood Advances

Self Cite

View full text Add to dashboard Cite

show abstract

“…To verify whether the generalized systemic neutrophilia in the periphery and within organs was due to increased granulopoiesis in the bone marrow, we performed detailed analysis of bone marrow from THP +/+ and THP 2/2 mice using flow cytometry as described [28][29][30] and shown in Figure 3, Supplemental Figure 2. Figure 3A shows a significant decrease in the marrow of THP 2/2 mice of two classes of granulocyte progenitor cells: common myeloid progenitors and granulocyte-macrophage progenitors.…”

Section: Thp Deficiency Causes Enhanced Granulopoiesis In the Bone Mamentioning

confidence: 99%

Tamm-Horsfall Protein Regulates Granulopoiesis and Systemic Neutrophil Homeostasis

Micanovic¹,

Chitteti

Dagher³

et al. 2015

Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

Tamm-Horsfall protein (THP) is a glycoprotein uniquely expressed in the kidney. We recently showed an important role for THP in mediating tubular cross-talk in the outer medulla and in suppressing neutrophil infiltration after kidney injury. However, it remains unclear whether THP has a broader role in neutrophil homeostasis. In this study, we show that THP deficiency in mice increases the number of neutrophils, not only in the kidney but also in the circulation and in the liver, through enhanced granulopoiesis in the bone marrow. Using multiplex ELISA, we identified IL-17 as a key granulopoietic cytokine specifically upregulated in the kidneys but not in the liver of THP 2/2 mice. Indeed, neutralization of IL-17 in THP 2/2 mice completely reversed the systemic neutrophilia. Furthermore, IL-23 was also elevated in THP 2/2 kidneys. We performed real-time PCR on laser microdissected tubular segments and FACS-sorted renal immune cells and identified the S3 proximal segments, but not renal macrophages, as a major source of increased IL-23 synthesis. In conclusion, we show that THP deficiency stimulates proximal epithelial activation of the IL-23/IL-17 axis and systemic neutrophilia. Our findings provide evidence that the kidney epithelium in the outer medulla can regulate granulopoiesis. When this novel function is added to its known role in erythropoiesis, the kidney emerges as an important regulator of the hematopoietic system.

show abstract

“…To confirm these data, the osteoblast progenitor populations were assessed by flow cytometric analysis. FACS-based analysis of live (7-AAD 38,39 ( Figure 4C) BM cells demonstrated a significant twofold increase in osteoblasts in TG Rac1 D/D Rac3 2/2 compared with WT mice ( Figure 4D). These findings were further supported by an increase in RNA expression levels of the osteoblast markers osteopontin (Opn) ( Figure 4E), alkaline phosphatase (ALP) (supplemental Figure 3B), and Runx2 (supplemental Figure 3C) …”

Section: The Vascular Endothelial Niche Is Regulated By Rac Proteinsmentioning

confidence: 99%

Perivascular deletion of murine Rac reverses the ratio of marrow arterioles and sinusoid vessels and alters hematopoiesis in vivo

Ciuculescu

Park

Canty

et al. 2015

Blood

View full text Add to dashboard Cite

• Rac deletion in Nestin 1 cells reverses the arteriolar-tosinusoid ratio in marrow.• demonstrated a marked decrease in arterioles and an increase in the number and volume of venous sinusoids in the marrow that was associated with a reduction in the numbers of immunophenotypically and functionally-defined long-term HSCs in the marrow, a decrease in colony-forming cells and a reduction in circulating progenitors. Rac-deleted animals demonstrated a significant increase in trabecular bone. These data demonstrate that Rac GTPases play an important role in the integrity of perivascular space. Increased trabecular bone and sinusoidal space and decreased arteriolar volume in this model were associated with decreased HSC, underscoring the complexity of regulation of hematopoiesis in the perivascular space. (Blood. 2015;125(20):3105-3113)

show abstract

CD166 regulates human and murine hematopoietic stem cells and the hematopoietic niche

Abstract: Key Points• CD166 identifies human and murine long-term repopulating stem cells.• CD166 is a functional marker of stem cells and the hematopoietic niche.We previously showed that immature CD166

Cited by 59 publications

References 39 publications

Osteomacs interact with megakaryocytes and osteoblasts to regulate murine hematopoietic stem cell function

Osteomacs interact with megakaryocytes and osteoblasts to regulate murine hematopoietic stem cell function

Tamm-Horsfall Protein Regulates Granulopoiesis and Systemic Neutrophil Homeostasis

Perivascular deletion of murine Rac reverses the ratio of marrow arterioles and sinusoid vessels and alters hematopoiesis in vivo

Contact Info

Product

Resources

About