Search

Since the huge success of bone marrow transplantation technology in clinical practice, hematopoietic stem cells (HSCs) have become the gold standard for defining the properties of adult stem cells (ASCs). Here, we describe the "self-renewal, multi-lineage differentiation, apoptosis, rest, and trafficking" or "SMART" model, which has been developed based on data derived from studies of HSCs as the most well-characterized stem cell type. Given the potential therapeutic applications of ASCs, we delineate the key characteristics of HSCs using this model and speculate on the physiological relevance of stem cells identified in other tissues. Great strides are being made in understanding the biology of ASCs, and efforts are now underway to develop safe and effective ASC-based therapies in this emerging area.

The isothiourea-catalyzed enantioselective construction of tertiary α-fluoro stereogenic centers has been demonstrated by using branched alkynyl-substituted acetic acids as starting materials, providing a broad range of optically active tertiary α-alkyl fluorides in high enantioselectivity (up to 97%

Hematopoietic differentiation is controlled by both genetic and epigenetic regulators. Long noncoding RNAs (lncRNAs) have been demonstrated to be important for normal hematopoiesis, but their function in erythropoiesis needs to be further explored. We profiled the transcriptomes of 16 murine hematopoietic cell populations by deep RNA sequencing and identified a novel lncRNA, Gm15915, that was highly expressed in erythroid-related progenitors and erythrocytes. For this reason, we named it lncEry. We also identified a novel lncEry isoform, which was the principal transcript that has not been reported before. lncEry depletion impaired erythropoiesis, indicating the important role of the lncRNA in regulating erythroid differentiation and maturation. Mechanistically, we found that lncEry interacted with WD repeat–containing protein 82 (WDR82) to promote the transcription of Klf1 and globin genes and thus control the early and late stages of erythropoiesis, respectively. These findings identified lncEry as an important player in the transcriptional regulation of erythropoiesis.

Hematopoietic differentiation is controlled by both genetic and epigenetic regulators. Long non-coding RNAs (lncRNAs) have been demonstrated to be important for normal hematopoiesis, but their function in erythropoiesis needs to be further explored. We profiled the transcriptomes of 16 murine hematopoietic cell populations by deep RNA-sequencing and identified a novel lncRNA, Gm15915, that was highly expressed in erythroid-related progenitors and erythrocytes. For this reason, we named it lncEry. We also identified a novel lncEry isoform, which was also the principal transcript that has not been reported before. LncEry depletion impaired erythropoiesis, indicating the important role of the lncRNA in regulating erythroid differentiation and maturation. Mechanistically, we found that lncEry interacted with WD repeat-containing protein 82 (WDR82) to promote the transcription of Klf1 and globin genes and thus control the early and late stages of erythropoiesis, respectively. These findings identified lncEry as an important player in the transcriptional regulation of erythropoiesis.

Planar chiral [2.2]paracyclophane-based isothiourea catalysts have been prepared over a few simple steps in high yields. In the presence of these catalysts, highly efficient catalytic enantioselective fluorination of carboxylic acids has been accomplished, providing a broad range of optically active α-fluoroesters in high yield and excellent enantioselectivity.

An asymmetric [2+2] annulation reaction through direct α-carbon functionalization of simple aldehydes via oxidative N-heterocyclic carbene catalysis is disclosed. These in situ generated triazolium enolate intermediates undergo a highly stereoselective Mannich reaction with isatin-derived ketimines followed by intramolecular lactamization to afford enantioenriched spirooxindole β-lactams bearing two vicinal stereogenic centers.

A 1-hydroxybenzotriazole-assisted, N-heterocyclic carbene catalyzed direct β-functionalization of saturated carboxylic esters is disclosed. This formal [3 + 2] annulation reaction of carboxylic esters with isatins affords optically pure spirooxindole lactones (on gram scale) bearing two vicinal stereogenic centers. A dual role of HOBt is proposed based on controlled experiments to rationalize the enhancement of diastereoselectivity and enantioselectivity.

An efficient asymmetric [2 + 3] annulation of simple aldehydes with N,N′-cyclic azomethine imines via oxidative N-heterocyclic carbene (NHC) catalysis is disclosed, affording bicyclic pyrazolidinones bearing two vicinal tertiary stereogenic centers with moderate to good yields (56–84% for 19 examples), good to excellent diastereoselectivities (>20:1 for 17 examples), and good to excellent enantioselectivities (66–98% for 19 examples). This direct α-carbon functionalization reaction of aldehyde can be readily performed on gram scale under mild conditions, and a five-membered transition state is proposed to rationalize the stereochemical outcome.

An efficient [4 + 3] annulation of 2-(1-tosylalkyl)phenols with C,N-cyclic azomethine imines via in situ generation of ortho-quinone methides (o-QMs) under mild basic reaction conditions is disclosed, furnishing biologically interesting seven-membered heterocyclic compounds with moderate to good yields and excellent diastereoselectivities. A gram-scale reaction is performed to demonstrate the potential in industrial application and two transition states are proposed to rationalize the outstanding diastereoselectivity.

An efficient strategy for the in situ generation of heterocyclic ortho-quinodimethanes (oQDMs) from 2-methyl-heteroarene-3-carboxylic esters by N-heterocyclic carbene (NHC) catalysis is disclosed. These heterocyclic oQDMs undergo highly enantioselective [4 + 2] annulation reactions with isatin-derived ketimines to afford optically pure heteroarene-fused δ-lactams bearing a quaternary stereogenic center. The main features of this reaction include challenging direct C(sp3)–H bond functionalizations, excellent enantioselectivities, readily available starting materials, mild reaction conditions, high efficiency, and operational simplicity.

An efficient strategy for the in situ generation of heterocyclic ortho-quinodimethanes (oQDMs) from 2-methyl-heteroarene-3-carboxylic esters by N-heterocyclic carbene (NHC) catalysis is disclosed. These heterocyclic oQDMs undergo highly enantioselective [4 + 2] annulation reactions with isatin-derived ketimines to afford optically pure heteroarene-fused δ-lactams bearing a quaternary stereogenic center. The main features of this reaction include challenging direct C(sp(3))-H bond functionalizations, excellent enantioselectivities, readily available starting materials, mild reaction conditions, high efficiency, and operational simplicity.